Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase

In mice homozygous for the 'viable motheaten' ( me^v ) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peritoneal cavity of the me^v mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other peripheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These abnormalities in development and differentiation of macrophages and dendritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnormal microenvironments, (either constitutive or in response to inflammatory stimuli) in the haematopoietic and lymphopoietic organs and tissues of these mice.     

Chronic effects of oral prostacyclin analogue on thromboxane A and prostacyclin metabolites in pulmonary hypertension

Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in patients with primary pulmonary hypertension and secondary pulmonary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The chronic effects of an oral prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plasma concentrations of thromboxane B, and 6-keto-prostaglandin F1_α were measured, as was the urinary excretion of 11-dehydro-thromboxane B, and 2.3-dinor-6-keto-prostaglandin F1_α, which are stable metabolites of thromboxane A, and prostacyclin, respectively. In patients with pulmonary hypertension, the plasma concentration of thromboxane B. and the ratio of thromboxane B, to 6-keto-prostaglandin F1_α were greater than in healthy controls: 210 ± 49 versus 28 ± 4 pg/mL (P<6.05) and 32.6 ± 8.9 versus 5.7± 1.8 (p<0.01), respectively. After 3 months of administration of beraprost. the plasma concentration of thromboxane B, and the ratio of thromboxane B, to 6-keto-prostaglandin F were reduced significantly: 210 ± 49 to 98 ± 26 pg/mL (P < 0.01) and 32.6 ± 8.9 to 18.0 ± 6.7 (P < 0.05). respectively. In contrast, the plasma concentrations of 6-keto-prostaglandin F in patients were slightly but not significantly higher than in controls, and did not change significantly after administration of beraprost. The concentrations of 11-dehydro-thromboxane B, and 2.3-dinor-6-keto-prostaglandin F, in urine correlated significantly with thromboxane B, and 6-keto-prostaglandin F . respectively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasculature.     

Assessment of variables affecting flow propagation velocity of the left ventricle in healthy children

BACKGROUND: The purpose of the present study was to establish the normal values of flow propagation velocity (FPV) in healthy children and examine the variables that affect FPV in clinical situations. METHODS: Two hundred and thirty- five healthy children and adolescents were assessed (aged 0-22.6 years, mean age 7.4 +/- 5.4 years; male, n = 142; female, n = 93). FPV was obtained from an apical four-chamber view and determined as the slope of aliasing velocity of early diastolic transmitral flow on the color M-mode using Aloka SSD-5500 with 5.0 MHz transducer. Aliasing velocity was set at 50-70% of the peak transmitral flow velocity. Peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), and the ratio of early to late peak velocity (E/A) were obtained. Tei index was also measured for analysis of general left ventricular performance. Left ventricular mass index (LVMI) was obtained from conventional echo measurement. E, E/A, Tei index and LVMI were compared with FPV in healthy subjects. RESULTS: FPV obtained from all subjects ranged from 23.7 to 96.0 cm/s (61.3 +/- 13.6 cm/s). Normal value of FPV was less dependent on age, body size, heart rate and left ventricular dimension. In contrast, although there was no significant correlation between FPV and ejection fraction, statistically significant correlation was found between FPV, LVMI (P = 0.0008) and Tei index (P = 0.025). CONCLUSIONS: FPV is independent of age, body size and heart rate and is useful to assess left ventricular relaxation in children.