BackgroundAtherosclerotic abdominal aortic aneurysm (AAA) is a progressive, gradual aortic rupture that results in death in the absence of surgical intervention. Key factors that regulate initiation and progression of AAA are unknown, making targeted interventions difficult. MicroRNAs play a fundamental role in atherosclerosis, and atherosclerotic coronary artery disease is characterized by tissue- and plasma-specific microRNA signatures. However, little is known about microRNAs involved in AAA pathology. This study examined tissue and plasma microRNAs specifically associated with AAA.Methods and ResultsAAA and normal wall tissues were sampled from patients undergoing AAA repair (n=13; mean age, 68±6 years) and aortic valve replacement surgery (n=7; mean age, 66±4 years), respectively. MicroRNA expression was assessed by high-throughput microRNA arrays and validated by real-time polymerase chain reaction for individual microRNAs that showed significant expression differences in the initial screening. MicroRNAs related to fibrosis (miR-29b), inflammation (miR-124a, miR-146a, miR-155, and miR-223), and endothelium (miR-126, let-7 family members, and miR-21) were significantly upregulated in AAA tissue. Significant negative correlations were seen in expression levels of monocyte chemoattractant protein-1 and miR-124a, -146a, and -223; tumor necrosis factor-α and miR-126 and -223; and transforming growth factor-β and miR-146a. Expression of microRNAs, such as miR-29b, miR-124a, miR-155, and miR-223, that were upregulated in AAA tissue was significantly reduced in plasma of patients with AAA (n=23; mean age, 72±9 years) compared to healthy controls (n=12; mean age, 51±11 years) and patients with coronary artery disease (n=17; mean age, 71±9 years).ConclusionsThe expression of some microRNAs was specifically upregulated in AAA tissue, warranting further studies on the microRNA function in AAA pathogenesis and on the possibility of using a microRNA biomarker for AAA diagnosis.

An experimental model for human T lymphocyte development from hemopoietic stem cells is necessary to study the complex processes of T cell differentiation in vivo. In this study, we report a newly developed nonobese diabetic (NOD)/Shi-scid, IL-2Rγ null (NOD/SCID/γcnull) mouse model for human T lymphopoiesis. When these mice were transplanted with human cord blood CD34+ cells, the mice reproductively developed human T cells in their thymus and migrated into peripheral lymphoid organs. Furthermore, these T cells bear polyclonal TCR-αβ, and respond not only to mitogenic stimuli, such as PHA and IL-2, but to allogenic human cells. These results indicate that functional human T lymphocytes can be reconstituted from CD34+ cells in NOD/SCID/γcnull mice. This newly developed mouse model is expected to become a useful tool for the analysis of human T lymphopoiesis and immune response, and an animal model for studying T lymphotropic viral infections, such as HIV.

Atorvastatin therapy at 20 mg/day provided a greater increase in fibrous cap thickness in coronary plaques compared with 5 mg/day of atorvastatin. The increase of fibrous cap was associated with the decrease in serum atherogenic lipoproteins and inflammatory biomarkers during atorvastatin therapy. (Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study; NCT00700037).

Long-term observation showed safety and good durability of the open stent-grafting technique for aortic arch disease. This technique could be an attractive treatment option for aortic arch aneurysm with distal extension and aortic dissection requiring aortic arch replacement.

Summary:infections early after BMT 3 and the late complication of vascular damage which may be caused by hypersensitivity to the conditioning agents 4 or interstitial lung disease. 5 Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneicObstructive lung disease (OLD) has been described as a serious complication after allogeneic BMT. The developbone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic ment of OLD was strongly associated with chronic GVHD. 6 Both clinical and histologic features of DC are very similar anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP misto that of chronic GVHD. 7 Additionally, some cases of DC have been reported to develop chronic pulmonary matched brother. He developed grade II acute graftversus-host disease (GVHD) and thereafter chronic disease. 8,9 We describe a case of DC with chronic restrictive lung disease 7 years after HLA-DP mismatched GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical allogeneic BMT, and report the results of immunological and histologic examination. improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effecCase report tive and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic A 1-year and 10 months-old boy was referred to our hospital because of epistaxis. He was the third child of healthy infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the parents, and there was no family history of skin or hematological disorders. He was noted to have reticular pigmenskin and the liver. These findings raise the possibility that this pulmonary complication was associated with tation and progressive nail dystrophy of both fingers and toes. He also had a congenital visual defect of the left eye. DC itself. Keywords: dyskeratosis congenita; allogeneic bone A brain CT scan showed bilateral parieto-occipital calcifications. Leukoplakia of the oral mucous membrane was not marrow transplantation; chronic GVHD; restrictive lung disease observed. Laboratory data revealed a hemoglobin of 5.4 g/dl, white blood cell count of 3.8 × 10 9 /l (absolute neutrophil count of 1.4 × 10 9 /l), and a platelet count of 19 × 10 9 /l. Bone marrow aspiration showed hypoplasia of Dyskeratosis congenita is a rare hereditary disorder characall cell lineages, and the number of hematopoietic progeniterized by reticular hyperpigmentation of the skin, dystor cells was reduced in colony assay. Cytogenetic studies trophy of the nails, and leukoplakia of mucosal memwere normal and there were no chromosomal breaks. branes. 1 It is frequently associated with severe aplastic Because treatment with anabolic steroids and prednisolone anemia and malignant...

BackgroundEpithelial mesenchymal transition (EMT) is thought to be an essential feature of malignant tumor cells when they spread into the stroma. Despite the extracellular acidity of tumor tissues, the effect of acidic extracellular pH (pHe) on EMT in carcinoma models, including the Lewis lung carcinoma (LLC) model, remains unclear.MethodsHigh and low metastatic LLC variants were generated by repeated tail vein injection of metastatic cells. DMEM/F12 medium, which has been supplemented with 15 mM HEPES, 4 mM phosphoric acid, and 1 g/L NaHCO3 and adjusted to the desire pH with HCl or NaOH, was used for cell culture. EMT marker gene expression was determined by quantitative reverse transcription-polymerase chain reaction. Migration and invasion activities were analyzed by wound healing assay and the Boyden chamber assay through Matrigel®, respectively.ResultsLow metastatic variant LLCm1 cells showed a cobble-stone like morphology at pHe 7.4. At pHe 6.8, however, their morphology became fibroblastic, similar in shape to high metastatic variant LLCm4 cells. Steady state levels of matrix metalloproteinase-9 (Mmp9) mRNA were induced by acidic pHe, maximizing at pH 6.8, with the levels of Mmp9 mRNA higher in LLCm4 than in LLCm1 cells. Both variants showed decreased levels of E-cadherin and increased levels of vimentin at pHe 6.8. Acidic pHe also induced expression of mRNAs encoding the E-cadherin repressors, Zeb2, Twist1 and Twist2, as well as enhancing cell motility and in vitro invasion through Matrigel®.ConclusionsAcidic pHe can induce EMT in some types of carcinoma.

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