In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

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.     

Decreasing one-year mortality and hospitalization rates for heart failure in Sweden; Data from the Swedish Hospital Discharge Registry 1988 to 2000.

AIMS: To investigate if improved treatment of coronary heart disease and hypertension, the major causes of chronic heart failure (CHF), in the last 20 years has had an impact on the incidence of CHF and survival. METHODS: National Swedish registers on hospital discharges and cause-specific deaths were used to calculate age- and sex-specific trends and sex ratios for heart failure admissions and deaths. The study included all men and women 45 to 84 years old hospitalized for the first time for heart failure in 19 Swedish counties between 1988 and 2000, a mean annual population 2.9 million. A total of 156?919 hospital discharges were included. RESULT: In 1988, a total of 267 men and 205 women per 100?000 inhabitants (age adjusted) were discharged for the first time with a principal diagnosis of heart failure. After 1993 a yearly decrease was observed, with 237 men and 171 women per 100?000 inhabitants discharged during 2000. The 30-day mortality decreased significantly. The decrease in 1-year mortality was more pronounced in the younger age groups, with a total reduction in mortality of 69% among men and 80% among women aged 45-54 years. The annual decrease was 9% among men and 10% among women aged 45-54 years (95% CI -7% to -12% and -6% to -14% respectively) and 4% among men and 5% among women (95% CI -4% to -5% for both) aged 75-84 years. CONCLUSION: The decrease in incidence and improved prognosis after a first hospitalization for heart failure coincides with the establishment of ACE-inhibitor therapy, the introduction of beta-blockers for treatment of heart failure, home-care programmes for heart failure, and more effective treatment and prevention of underlying diseases. Notwithstanding, despite considerable improvement, 1-year mortality after a first hospitalization for heart failure is still high.