Appearance of large scavenger receptor A-positive cells in peripheral blood: A potential risk factor for severe exacerbation of chronic obstructive pulmonary disease.

Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined. Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed-up for 1 year. Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation. Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation. The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A. The Kaplan-Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively. The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation.

Easy detection of hormone secretion from LßT2 cells by using Gaussia luciferase.

Reproduction is regulated by gonadotropins secreted from gonadotrophs. The production and secretion of gonadotropins are mainly regulated by gonadotropin-releasing hormone (GnRH). Agonists or antagonists that influence GnRH action on gonadotrophs are important to regulate reproduction; however, these factors have not been fully characterized due to the lack of simple and easy-to-use techniques to detect gonadotropin secretion from gonadotropin-producing cells. In the present study, we found that Gaussia luciferase (Gluc), which was expressed in LßT2 cells, can be secreted like a luteinizing-hormone (LH) upon stimulation with GnRH. The Gluc secreted into the medium was easily monitored as luminescence signals. The detection range of the GnRH-induced Gluc activity was comparable to that of the enzyme-linked immunosorbent assay for LH. In addition, when the Gluc was expressed in AtT20 cells, which produce adrenocorticotropic hormone (ACTH), the Gluc activity in the medium increased in parallel with the ACTH secretion upon stimulation with corticotropin-releasing hormone. Thus, the Gluc assay in the present study can be easily used for high-throughput screening of factors that influence LH or ACTH secretion from LßT2 or AtT20 cells, respectively.

Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment.

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174(th) position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A.

Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors.

Minute lesions of alveolar damage in lungs of patients with stable idiopathic pulmonary fibrosis.

AIMS: To investigate the mechanisms underlying the acute exacerbation of idiopathic pulmonary fibrosis, and in particular the role of minute lesions of alveolar damage. METHODS AND RESULTS: We examined surgical lung biopsy samples from 38 patients with stable idiopathic pulmonary fibrosis, and evaluated the association between the foci and development of acute exacerbation. Mild extravasation, probably resulting from lung injury and intra-alveolar oedema fluid, were observed in narrow areas of architecturally intact lung tissue. Minute lesions of alveolar damage were detected in these areas. Alveolar epithelial cells in these lesions were injured. Hypoxia-inducible factor-2α-positive macrophages, tumour necrosis factor-α-positive macrophages and neutrophils had accumulated in alveolar spaces in and around these lesions. Cases were classified into patients without (17) and with (21) minute lesions of alveolar damage. Development to acute exacerbation (five cases) occurred only in patients with minute lesions of alveolar damage (P = 0.03). CONCLUSIONS: The formation of minute lesions of alveolar damage may be initiated by hypoxia, and such lesions play important roles in the development of acute exacerbation.

New Surgical Drapes for Observation of the Lower Extremities during Abdominal Aortic Repair.

OBJECTIVE: For the early diagnosis and therapy of peripheral thromboembolism (TE) as a complication of abdominal aortic repair (AAR), we developed and evaluated the usefulness of surgical drapes that permit observation of the lower extremities during AAR. MATERIALS AND METHODS: Between January 2007 and June 2009, the handling, durability, and usefulness of new surgical drapes were evaluated during AAR in 157 patients with abdominal aortic aneurysms and 9 patients with peripheral arterial disease. The drapes are manufactured by Hogy Medical Co. Ltd. and made of a water-repellent, spun lace, non-woven fabric, including a transparent polyethylene film that covers the patients' legs. This transparent film enables inspection and palpation of the lower extremities during surgery for early diagnosis and therapy of peripheral TE. RESULTS: As a peripheral complication, 1 patient had right lower extremity TE. This was diagnosed immediately after anastomosis, thrombectomy was performed, and the remaining clinical course was uneventful. In all patients, the drapes permitted observation of the lower extremities , and the dorsal arteries were palpable. There were no problems with durability. CONCLUSIONS: New surgical drapes permit observation of the lower extremities during AAR for early diagnosis and treatment of peripheral TE.

Hybrid treatment of multiple aortic aneurysms by combined conventional surgery and endovascular aortic repair.

PURPOSE: We evaluated the operative results of our treatment for multiple aortic aneurysms by means of a hybrid procedure consisting of a combination of conventional surgical maneuvers and simultaneous or sequential endovascular aortic repair (EVAR). MATERIALS AND METHODS: From August 1998 to April 2007, a total of 15 patients, 11 men and 4 women, ranging in age from 62 to 78 years, were treated with hybrid procedures for multiple aortic aneurysms. The pathology of these patients were, atherosclerotic aneurysm in 12 patients, atherosclerotic aneurysm associated with chronic dissection in 2 and type III chronic dissection in 1 patient. The distribution of aneurysmal locations were as follows: 5 patients had aneurysms at the arch and descending aorta, 1 had at the arch and thoracoabdominal aorta, 6 at the descending and abdominal aorta. Two patients with chronic dissection had simultaneous abdominal aortic aneurysms. In all except 1 of the 7 patients who had abdominal aortic aneurysm, we performed abdominal aneurysmectomy and EVAR simultaneously. In 7 patients, EVAR was performed sequentially after graft replacement surgery. In 2 patients, EVAR was the initial procedure followed by conventional surgery. The mean interval between first and second stage procedures was approximately 4 months. RESULTS: One patients died of methicillin resistant Staphylococcus aureus pneumonia 3 months after the simultaneous procedure, all others were discharged and survive. In particular, no major EVAR linked complication was observed in the follow-up period (range 3 to 91 months, mean 46 months). CONCLUSION: The hybrid procedure for the treatment of multiple aortic aneurysmal disease is less invasive compared to conventional staged surgery and the outcome in terms of mortality and morbidity in hospital as well as long-term follow-up are satisfactory.