Quantitative analysis of lung perfusion in patients with primary pulmonary hypertension.

The aim of this study was to evaluate quantitatively the heterogeneity of lung perfusion scans in patients with primary pulmonary hypertension (PPH) and to compare it with the severity of disease. METHODS: Lung perfusion scans were obtained on 22 patients with PPH and 12 age-matched control subjects. The perfused area rates (PARs) were calculated by dividing the lung area in each 10% threshold width from 10% to 100% of maximal counts by total lung area. The total absolute difference in the PAR between each patient and the mean control value was assumed as the perfusion index of the lung (P index). The P index was compared with hemodynamic parameters and the right ventricular ejection fraction (RVEF), including 7 patients who received long-term vasodilator therapy. RESULTS: The P index correlated significantly with mean pulmonary arterial pressure (P < 0.001) and RVEF (P < 0.05). In patients with vasodilator therapy, the P index was improved significantly after therapy (P < 0.05) and was associated with a reduction in pulmonary arterial pressure. CONCLUSION: Quantitative assessment of lung perfusion irregularity might provide useful information about the severity of disease and the effect of therapy in addition to the routine visual representation.     

Effect of hypoxia on gene expression of bone marrow-derived mesenchymal stem cells and mononuclear cells

MSC have self-renewal and multilineage differentiation potential, including differentiation into endothelial cells and vascular smooth muscle cells. Although bone marrow-derived mononuclear cells (MNC) have been applied for therapeutic angiogenesis in ischemic tissue, little information is available regarding comparison of the molecular foundation between MNC and their MSC subpopulation, as well as their response to ischemic conditions. Thus, we investigated the gene expression profiles between MSC and MNC of rat bone marrow under normoxia and hypoxia using a microarray containing 31,099 genes. In normoxia, 2,232 (7.2%) and 2,193 genes (7.1%) were preferentially expressed more than threefold in MSC and MNC, respectively, and MSC expressed a number of genes involved in development, morphogenesis, cell adhesion, and proliferation, whereas various genes highly expressed in MNC were involved in inflammatory response and chemotaxis. Under hypoxia, 135 (0.44%) and 49 (0.16%) genes were upregulated (>threefold) in MSC and MNC, respectively, and a large number of those upregulated genes were involved in glycolysis and metabolism. Focusing on genes encoding secretory proteins, the upregulated genes in MSC under hypoxia included several molecules involved in cell proliferation and survival, such as vascular endothelial growth factor-D, placenta growth factor, pre-B-cell colony-enhancing factor 1, heparin-binding epidermal growth factor-like growth factor, and matrix metalloproteinase-9, whereas the upregulated genes in MNC under hypoxia included proinflammatory cytokines such as chemokine (C-X-C motif) ligand 2 and interleukin-1alpha. Our results may provide information on the differential molecular mechanisms regulating the properties of MSC and MNC under ischemic conditions. Disclosure of potential conflicts of interest is found at the end of this article.     

Selective adsorption of human CD4 T cells

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.     

Increase in thrombomodulin concentrations after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension

STUDY OBJECTIVES: The objectives of the study were as follows: (1) to identify differences in endothelial dysfunction and altered hemostasis in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared with patients with acute pulmonary thromboembolism (APTE) uncomplicated by pulmonary arterial hypertension, by measuring the concentrations of thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, and other plasma factors of coagulation and fibrinolysis; and (2) to examine the effects of thromboendarterectomy on TM levels as a parameter of endothelial cell injury leading to abnormal hemostasis as well as to examine the clinical significance of TM as a marker of endothelial injury. DESIGN: Prospective comparison of concentrations of TM and other plasma parameters among patients with CTEPH or APTE and control subjects. PARTICIPANTS: We studied 22 healthy subjects (ie, control subjects), 22 patients who had been clinically stabilized after APTE, and 44 patients with CTEPH. In 21 of the patients with CTEPH, measurements were repeated after they had undergone pulmonary thromboendarterectomy. MEASUREMENTS AND RESULTS: Plasma concentrations of soluble TM in patients with CTEPH were measured and compared with those in patients with APTE. The mean (+/- SD) TM concentration in the CTEPH group (2.5 +/- 0.7 ng/mL) was significantly lower than that in the control group (4.0 +/- 0.6 ng/mL; p < 0.05). In contrast, the mean plasma TM concentration in the APTE group (4.6 +/- 1.9 ng/mL) was similar to that in the control group. After patients underwent pulmonary thromboendarterectomy, the mean TM concentration increased from 2.0 +/- 0.4 to 2.9 +/- 0.7 ng/mL (p < 0.05). In the CTEPH group, the plasma TM concentration was negatively correlated with mean pulmonary arterial pressure and total pulmonary resistance (p < 0.05). CONCLUSIONS: A decreased plasma TM concentration may reflect pulmonary vascular endothelial dysfunction leading to altered anticoagulant and fibrinolytic function in CTEPH, which rarely develops after APTE. Plasma TM measurements may be useful in distinguishing CTEPH with severe pulmonary hypertension from recurrent APTE.