Detection of abundant megakaryocytes in pulmonary artery blood in lung cancer patients using a microfluidic platform.

OBJECTIVES: The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation. MATERIALS AND METHODS: We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry. RESULTS: Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue. CONCLUSIONS: These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients.

Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese.

BACKGROUND: In our previous study, a marked association between Helicobacter pylori seropositivity and functional polymorphisms of the secretor and Lewis genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14-0.70 for se/se genotype relative to Se/Se genotype; and OR, 10.3; 95% CI, 3.16-33.8 for high-risk group defined by the combination of Se and Le relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC) undergoing gastroscopy at Aichi Cancer Center Hospital. METHODS: The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city. RESULTS: The associations between H. pylori seropositivity and the Se and Le genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00-2.32 for se/se genotype relative to Se/Se genotype; and OR, 0.77; 95% CI, 0.43-1.40 for the high-risk group defined similarly to the previous study), and among the HCE (OR, 1.25; 95% CI, 0.75-2.07; and OR, 1.07; 95% CI, 0.50-2.26, respectively). The discrepancy between the previous and present results was not explained by the difference in the distributions of age, sex, smoking, and H. pylori seroprevalence. CONCLUSION: Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important to understand the whole picture of the association under study.