Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease

Background: Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34+ progenitor cells to examine whether these genes are associated with COPD development. Methods: This study included 358 patients with a smoking history of more than 10 pack-years. RNA was extracted from blood samples and from CD34+ progenitor cells treated with cigarette smoke extract (CSE), followed by assessment of CD31, CD34, Sirt1 mRNA, miR-34a, and miR-126-3p expression by real-time RT-PCR. Results: The expression of CD31, CD34, Sirt1 mRNAs, and miR-126-3p decreased and that of miR-34a increased in moderate COPD compared with that in control smokers. However, no significant differences in these genes were observed in blood cells from patients with severe COPD compared with those in control smokers. CSE significantly decreased Sirt1 and increased miR-34a expression in cultured progenitor cells. Conclusion: Sirt1 expression in blood cells from patients with COPD could be a biomarker for disease stability in patients with moderate COPD. MiR-34a may participate in apoptosis and/or senescence of EPCs in smokers. Decreased expression of CD31, CD34, and miR-126-3p potentially represents decreased numbers of EPCs in blood cell from patients with COPD

Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient's response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discusse

Whole-rock chemical compositions of granitic dykes in western part of the Sør Rondane Mountains, East Antarctica

第6回極域科学シンポジウム[OG] 地圏11月16日（月）　国立極地研究所１階交流アトリウ

Late Proterozoic juvenile arc metatonalite and adakitic granitoids in the Sør Rondane Mountains, East Antarctica

第3回極域科学シンポジウム/第32回極域地学シンポジウム 11月30日（金） 国立極地研究所 ３階ラウン

Rab38 Mutation and the Lung Phenotype

Rab38 is highly expressed in alveolar type II cells, melanocytes, and platelets. These cells are specifically-differentiated cells and contain characteristic intracellular organelles called lysosome-related organelles, i.e., lamellar bodies in alveolar type II cells, melanosomes in melanocytes, and dense granules in platelets. There are Rab38-mutant rodents, i.e., chocolate mice and Ruby rats. While chocolate mice only show oculocutaneous albinism, Ruby rats show oculocutaneous albinism and prolonged bleeding time and, hence, are a rat model of Hermansky-Pudlak syndrome (HPS). Most patients with HPS suffer from fatal interstitial pneumonia by middle age. The lungs of both chocolate mice and Ruby rats show remarkably increased amounts of lung surfactant and conspicuously enlarged lysosome-related organelles, i.e., lamellar bodies, which are also characteristic of the lungs in human HPS. There are 16 mutant HPS-mouse strains, of which ten mutant genes have been identified to be causative in patients with HPS thus far. The gene products of eight of the ten genes constitute one of the three protein complexes, i.e., biogenesis of lysosome-related organelle complex-1, -2, -3 (BLOC-1, -2, -3). Patients with HPS of the mutant BLOC-3 genotype develop interstitial pneumonia. Recently, BLOC-3 has been elucidated to be a guanine nucleotide exchange factor for Rab38. Growing evidence suggests that Rab38 is an additional candidate gene of human HPS that displays the lung phenotype

Rab38 Mutation and the Lung Phenotype

Rab38 is highly expressed in alveolar type II cells, melanocytes, and platelets. These cells are specifically-differentiated cells and contain characteristic intracellular organelles called lysosome-related organelles, i.e., lamellar bodies in alveolar type II cells, melanosomes in melanocytes, and dense granules in platelets. There are Rab38-mutant rodents, i.e., chocolate mice and Ruby rats. While chocolate mice only show oculocutaneous albinism, Ruby rats show oculocutaneous albinism and prolonged bleeding time and, hence, are a rat model of Hermansky-Pudlak syndrome (HPS). Most patients with HPS suffer from fatal interstitial pneumonia by middle age. The lungs of both chocolate mice and Ruby rats show remarkably increased amounts of lung surfactant and conspicuously enlarged lysosome-related organelles, i.e., lamellar bodies, which are also characteristic of the lungs in human HPS. There are 16 mutant HPS-mouse strains, of which ten mutant genes have been identified to be causative in patients with HPS thus far. The gene products of eight of the ten genes constitute one of the three protein complexes, i.e., biogenesis of lysosome-related organelle complex-1, -2, -3 (BLOC-1, -2, -3). Patients with HPS of the mutant BLOC-3 genotype develop interstitial pneumonia. Recently, BLOC-3 has been elucidated to be a guanine nucleotide exchange factor for Rab38. Growing evidence suggests that Rab38 is an additional candidate gene of human HPS that displays the lung phenotype