Publications by authors named "Shuichi Abe"

74 Publications

Efficacy of hybrid endoscopic submucosal dissection with SOUTEN in gastric lesions: An porcine model basic study.

World J Gastrointest Surg 2021 Jun;13(6):563-573

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Background: Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice.

Aim: To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an porcine model basic study.

Methods: Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and secondary outcomes were or complete resection, perforation, procedure time/speed for both, mucosal incision, and submucosal dissection. Factors associated with difficulty in ESD including longer procedure time, incomplete resection, and perforation, were also investigated. Categorical and continuous data were analyzed using the chi-square test or Fisher's exact test and the Mann-Whitney test, respectively.

Results: The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD (median: 8.3 min 16.2 min, < 0.001). Time, speed, and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD (time, 5.2 min 10.4 min, < 0.001; speed, 43.7 mm/min 23.8 mm/min, < 0.00; injection volume, 1.5 mL 3.0 mL, < 0.001), although no significant differences in those factors were observed between both groups during mucosal incision. There was also no significant difference between both groups in the /complete resection rate and perforation rate (complete resection, 93.8% 87.5%, = 0.67; perforation, 0% 3.1%, = 1). Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD (odds ratio = 10.2; highest among factors).

Conclusion: Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.
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http://dx.doi.org/10.4240/wjgs.v13.i6.563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223703PMC
June 2021

Clarithromycin As an Alternative and Prophylactic Agent in a Hematopoietic Stem Cell Transplantation Patient.

Am J Case Rep 2021 Jun 15;22:e931731. Epub 2021 Jun 15.

Medical Mycology Research Center, Chiba University, Chiba, Japan.

BACKGROUND Nocardia infections have rarely been reported in hematopoietic stem cell transplantation (HSCT) patients, who usually receive the prophylactic use of sulfamethoxazole/trimethoprim (ST) against Pneumocystis jiroveci. However, the ST prophylaxis, sensitive to Nocardia species, sometimes induces renal toxicities. Therefore, alternative prophylactic or therapeutic drugs are required for nocardiosis in HSCT patients. CASE REPORT A 34-year-old Japanese man with acute mixed phenotypic leukemia with t(9; 22) received allogenic peripheral blood HSCT from a haplo-identical sibling donor. He developed graft versus host disease (GVHD) with grade II, and was treated with prednisolone and cyclosporine A with concurrent ciprofloxacin, fluconazole, valacyclovir, and ST. However, the prophylactic ST was ceased because of its renal toxicity. He developed a pulmonary nodular lesion with elevated ß-D-glucan and Aspergillus galactomannan antigen. Repeated blood and sputum culture isolated no pathogens. Voriconazole treatment administered once improved these lesions and laboratory findings. One month later, he presented with right pleuritic chest pain and multiple ring-enhancing cavitation lesions along the ribs. A needle biopsy demonstrated Nocardia elegans, which is an extremely rare infection induced by Nocardia species, in the cavitation lesions, shown by 16S rRNA gene sequencing. He was started on doripenem and liposomal amphotericin B, and a subsequent treatment kept him free from Nocardia elegans infection, without any adverse effects, while continuing the cyclosporine A and prednisolone treatment for chronic GVHD. CONCLUSIONS Clarithromycin has fewer adverse effects than ST. This case suggests that clarithromycin is an appropriate alternative and prophylactic therapy for patients with nocardiosis and ST toxicities.
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http://dx.doi.org/10.12659/AJCR.931731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216568PMC
June 2021

Tracking COVID-19 with wastewater to understand asymptomatic transmission.

Int J Infect Dis 2021 May 11;108:296-299. Epub 2021 May 11.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Antimicrobial Resistance and Stewardship Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address:

Introduction: SARS-CoV-2 RNA is excreted in feces of most patients, therefore viral load in wastewater can be used as a surveillance tool to develop an early warning system to help and manage future pandemics.

Methods: We collected wastewater from 24 random locations at Bangkok city center and 26 nearby suburbs from July to December 2020. SARS-CoV-2 RNA copy numbers were measured using real-time polymerase chain reaction (PCR).

Results: SARS-CoV-2 RNA was detected in wastewater from both the city center and suburbs. Except for July, there were no significant differences in copy numbers between the city center and suburbs. Between October and November, a sharp rise in copy number was observed in both places followed by two to three times increase in December, related to SARS-CoV-2 cases reported for same month.

Conclusions: Our study provided the first dataset related to SARS-CoV-2 viral RNA in the wastewater of Bangkok. Our results suggest that wastewater could be used as a complementary source for detecting viral RNA and predicting upcoming outbreaks and waves.
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http://dx.doi.org/10.1016/j.ijid.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111879PMC
May 2021

Distribution and Variation of Serotypes and Pneumococcal Surface Protein A Clades of Strains Isolated From Adult Patients With Invasive Pneumococcal Disease in Japan.

Front Cell Infect Microbiol 2021 19;11:617573. Epub 2021 Mar 19.

Toyama Institute of Health, Toyama, Japan.

Pneumococcal surface protein A (PspA) is a surface protein of that may be a candidate antigen for new pneumococcal vaccines. This study investigates the distribution of PspA clades of the causative strains of adult invasive pneumococcal disease (IPD) in Japan. Of the 1,939 strains isolated from cases of adult IPD during 2014-2019, the PspA clades of 1,932 (99.6%) strains were determined, and no was detected in the remaining 7 strains (0.4%). PspA clades 1-6 were detected in 786 (40.5%), 291 (15.0%), 443 (22.8%), 369 (19.0%), 33 (1.7%), and 6 (0.3%) strains, respectively. New PspA clades (0.2%) were identified in two non-typeable and two serotype 35B pneumococci. The proportions of clade 1 and clade 2 showed significantly decreased and increased trends, respectively. Furthermore, the PspA clade of pneumococcal strains was partially serotype- and sequence type-dependent. The majority of strains belonging to serotypes contained in both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) belonged to PspA clades 1 or 3. In contrast, the distribution of clades in non-vaccine serotypes was wider than that of vaccine serotype pneumococci. Our findings demonstrate that almost all pneumococcal strains from adult IPD express PspA clades 1-4, especially for non-vaccine serotypes. These results may be useful for the development of a new pneumococcal vaccine with PspA.
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http://dx.doi.org/10.3389/fcimb.2021.617573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044978PMC
July 2021

Assistant skill in gastric endoscopic submucosal dissection using a clutch cutter.

World J Gastrointest Surg 2021 Feb;13(2):116-126

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan.

Background: A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection (ESD) for gastrointestinal tract tumors. The assistant during the ESD using a clutch cutter (ESD-C) needs to rotate the device and grasp the target tissue appropriately; therefore, the assistant's skill may affect the technical outcomes of ESD-C.

Aim: To determine how assistant skill level affected the technical outcomes of gastric ESD-C using an porcine training model.

Methods: In this pilot study, mock lesions of 15-30 mm in diameter were created in the middle or lower third of the porcine stomach. A total of 32 ESD-C procedures were performed by 16 trainees. Each trainee operator performed two ESD-C procedures; one ESD-C was assisted by an expert (ESD-C-E), and the other was assisted by a non-expert (ESD-C-NE). The total procedure time of the ESD was set as the primary outcome, and resection rate, complete procedure rate, perforation rate, and each procedure time/speed for mucosal incision or submucosal dissection were set as the secondary outcomes. In addition, we investigated factors associated with the difficulty of ESD including incompletion of ESD procedure, a long procedure time (≥ 20 min) or intraoperative perforation.

Results: The median total procedure time of the ESD-C-E was significantly shorter than that of the ESD-C-NE (12.9 min 21.9 min, = 0.001). The resection rate was 100% in both groups. Complete resection rates of the ESD-C-E and ESD-C-NE groups were 100% and 93.8%, respectively. No intraoperative perforation was observed in both groups. In the multivariate analysis, assistant skill was significantly associated with the difficulty of ESD, with the highest odds ratio of 16.5.

Conclusion: Assistance by an expert is an important factor when trainees perform ESD-C procedures.
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http://dx.doi.org/10.4240/wjgs.v13.i2.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898188PMC
February 2021

Functional analysis of human fibrocytes derived from monocytes reveals their profibrotic phenotype through paracrine effects.

J Med Invest 2020 ;67(1.2):102-112

Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Fibrocytes, which are bone marrow-derived collagen-producing cells, were reported to play a role in the pathogenesis of pulmonary fibrosis. However, their function in pulmonary fibrosis is unclear. We analyzed their function compared with that of monocytes and localization in fibrotic tissues in patients with idiopathic pulmonary fibrosis (IPF). We compared the gene expression profile of monocyte-derived fibrocytes with that of monocytes by microarray analysis. Proliferation and differentiation into myofibroblasts were examined by 3H-thymidine incorporation assay and Western blotting. We measured the level of growth factors in the culture supernatant of fibrocytes by ELISA. The localization of fibrocytes in lung tissues of patients with IPF was determined by immunofluorescence staining. Compared with monocytes, fibrocytes had higher expression of extracellular matrix- and growth factor-encoding genes, including PDGF-B, FGF-2 and VEGF-B. Although fibrocytes did not proliferate in response to PDGF, co-culture of fibrocytes stimulated the growth of lung fibroblasts through the production of PDGF-BB. In the lung of IPF patients, CD45+Collagen-I+FSP-1+ cells, which have a similar phenotype to fibrocytes, were detected and co-stained with anti-PDGF antibody. This study suggested that fibrocytes function in pulmonary fibrosis partly by producing PDGF in the lungs of IPF patients. J. Med. Invest. 67 : 102-112, February, 2020.
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http://dx.doi.org/10.2152/jmi.67.102DOI Listing
June 2021

The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice.

Exp Lung Res 2019 09 12;45(7):188-199. Epub 2019 Jul 12.

a Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University , Tokushima , Japan.

Wnt/β-catenin signaling was reported to be activated in pulmonary fibrosis, and was focused on as a target for antifibrotic therapy. However, the mechanism how the inhibition of Wnt/β-catenin signaling ameliorate pulmonary fibrosis has not been fully elucidated. The purpose of this study is to explore the target cells of Wnt/β-catenin inhibition in pulmonary fibrosis and to examine the antifibrotic effect of the novel inhibitor PRI-724 specifically disrupting the interaction of β-catenin and CBP. The effect of C-82, an active metabolite of PRI-724, on the expression of TGF-β1 and α-smooth muscle actin (SMA) was examined on fibroblasts and macrophages. We also examined the effects of PRI-724 in mouse model of bleomycin-induced pulmonary fibrosis. The activation and increased accumulation of β-catenin in the canonical pathway were detected in lung fibroblasts as well as macrophages stimulated by Wnt3a using Western blotting. Treatment with C-82 reduced CBP protein and increased p300 protein binding to β-catenin in the nucleus of lung fibroblasts. In addition, C-82 inhibited the expression of SMA in lung fibroblasts treated with TGF-β, indicating the inhibition of myofibroblast differentiation. In the fibrotic lungs induced by bleomycin, β-catenin was stained strongly in macrophages, but the staining of β-catenin in alveolar epithelial cells and fibroblasts was weak. The administration of PRI-724 ameliorated pulmonary fibrosis induced by bleomycin in mice when administered with a late, but not an early, treatment schedule. Analysis of bronchoalveolar fluid (BALF) showed a decreased number of alveolar macrophages. In addition, the level of TGF-β1 in BALF was decreased in mice treated with PRI-724. C-82 also inhibited the production of TGF-β1 by alveolar macrophages. These results suggest that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs.
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http://dx.doi.org/10.1080/01902148.2019.1638466DOI Listing
September 2019

Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice.

PLoS One 2018 31;13(12):e0209786. Epub 2018 Dec 31.

Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of pulmonary fibrosis. Nintedanib, a multi-kinase inhibitor that targets several tyrosine kinases, including PDGF receptor (PDGFR), was recently approved as an anti-fibrotic agent to reduce the deterioration of FVC in patients with idiopathic pulmonary fibrosis (IPF). However, the effects of PDGFR-α or -β on pulmonary fibrosis remain unclear. In an attempt to clarify their effects, we herein used blocking antibodies specific for PDGFR-α (APA5) and -β (APB5) in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. The effects of these treatments on the growth of lung fibroblasts were examined using the 3H-thymidine incorporation assay in vitro. The anti-fibrotic effects of these antibodies were investigated with the Ashcroft score and collagen content of lungs treated with BLM. Their effects on inflammatory cells in the lungs were also analyzed using bronchoalveolar lavage fluid. We investigated damage to epithelial cells and the proliferation of fibroblasts in the lungs. APA5 and APB5 inhibited the phosphorylation of PDGFR-α and -β as well as the proliferation of lung fibroblasts induced by PDGF-AA and BB. The administration of APB5, but not APA5 effectively inhibited BLM-induced pulmonary fibrosis in mice. Apoptosis and the proliferation of epithelial cells and fibroblasts were significantly decreased by the treatment with APB5, but not by APA5. The late treatment with APB5 also ameliorated fibrosis in lungs treated with BLM. These results suggest that PDGFR-α and -β exert different effects on BLM-induced pulmonary fibrosis in mice. A specific approach using the blocking antibody for PDGFR-β may be useful for the treatment of pulmonary fibrosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209786PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312310PMC
June 2019

Propensity score-matching analysis to compare clinical outcomes of endoscopic submucosal dissection for early gastric cancer in the postoperative and non-operative stomachs.

BMC Gastroenterol 2018 Aug 6;18(1):125. Epub 2018 Aug 6.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: Endoscopic submucosal dissection (ESD) of the postoperative stomach (ESD-P) for early gastric cancer (EGC) is considered a technically difficult procedure. However, it is difficult to compare the outcomes of ESD-P and ESD of the non-operative stomach (ESD-N) because their baseline characteristics are different. Therefore, we aimed to compare the technical outcomes of ESD-P with those of ESD-N using a propensity score-matching analysis to compensate for the differences.

Methods: The chart records of 1046 patients with EGC who were treated with ESD between January 2004 and July 2016 at Kitakyushu Municipal Medical Center in Japan were reviewed in this retrospective study. Multivariate analyses and propensity score-matching were performed for age, sex, lesion location, lesion size, tumor invasion, tumor size, ulcer (scar), and operator skill. The primary outcome was procedure time. Secondary outcomes were percentages of en bloc, complete, and curative resections, and percentages of adverse events, which were evaluated between the two groups.

Results: Forty-one patients were in the ESD-P group and 1005 patients were in the ESD-N group. Propensity score-matching created 41 matched pairs. According to the adjusted comparisons, ESD-P required a significantly longer procedure time (85 min vs 51 min, p < 0.001). Other treatment outcomes showed an en bloc resection rate of 100% for both groups (p = 1) and complete resection rates of 95.1 and 97.6% (p = 1), curative resection rates of 90.2 and 90.2% (p = 1), perforation during ESD rates of 2.4 and 0% (p = 1), and postprocedure bleeding rates of 2.4 and 2.4% (p = 1) for the ESD-P and ESD-N groups, respectively. For the ESD-P group, lesions on the suture line or anastomotic site were significantly associated with longer procedure times (p = 0.038).

Conclusions: ESD-P was a more time-consuming procedure than ESD-N. However, ESD-P and ESD-N achieved high rates of curative resection with a low rate of adverse events for the treatment of EGC. ESD could be selected as the treatment for EGC even in the postoperative stomach provided that careful attention is given to lesions on the suture line or anastomotic site.
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http://dx.doi.org/10.1186/s12876-018-0855-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080519PMC
August 2018

Splash M-knife versus Flush Knife BT in the technical outcomes of endoscopic submucosal dissection for early gastric cancer: a propensity score matching analysis.

BMC Gastroenterol 2018 Feb 27;18(1):35. Epub 2018 Feb 27.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer. A new multi-functional ESD device was developed to achieve complete ESD with a single device. A metal plate attached to its distal sheath achieves better hemostasis during the procedure than the other needle-knife device, Flush Knife BT®, that has been conventionally used. The aim of this study was to compare the technical outcomes of ESD for early gastric cancer using the Splash M-Knife® with those using the Flush Knife BT.

Methods: We conducted a retrospective review of the case records of 149 patients with early gastric cancer treated with ESD using the needle-type ESD knives between January 2012 and August 2016 at Kitakyushu Municipal Medical Center. Lesions treated with ESD using the Splash M-knife (ESD-M) and the Flush Knife BT (ESD-F) were compared. Multivariate analyses and propensity score matching were used to compensate for the differences in age, gender, underlying disease, antithrombotic drug use, lesion location, lesion position, macroscopic type, tumor size, presence of ulceration, operator level and types of electrosurgical unit used. The primary endpoint was the requirement to use hemostatic forceps in the two groups. The secondary endpoints of procedure time, en bloc and complete resection rates, and adverse events rates were evaluated for the two groups.

Results: There were 73 patients in the ESD-M group, and 76 patients in the ESD-F group. Propensity score matching analysis created 45 matched pairs. Adjusted comparisons between the two groups showed a significantly lower usage rate of hemostatic forceps in the ESD-M group than in the ESD-F group (6.7% vs 84.4%, p < 0.001). Treatment outcomes showed an en bloc resection rate of 100% in both groups; complete resection rate of 95.6% vs 100%, p = 0.49; median procedure time of 74.0 min vs 71.0 min, p = 0.90; post-procedure bleeding of 2.2% vs 2.2%, p = 1, in the ESD-M and ESD-F groups, respectively. There were no perforations in either group.

Conclusions: ESD-M appeared to reduce the usage of hemostatic forceps during ESD for early gastric cancer without increasing the adverse effects. Thus, it may contribute to a reduction in the total ESD cost.
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http://dx.doi.org/10.1186/s12876-018-0763-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832194PMC
February 2018

meningitis in a diffuse large B-cell lymphoma patient with CD4-positive lymphocytopenia and persistent oligoclonal CD8-positive lymphocytes in the peripheral blood.

Int J Clin Exp Pathol 2018 1;11(1):455-461. Epub 2018 Jan 1.

Medical Mycology Research Center, Chiba University Chuo-Ku, Chiba, Japan.

Nocardiosis, sometimes presenting with multiple granulomatous lesions, is a rare opportunistic infection occurring in immunocompromised patients. However, its immunological features remain largely unaddressed. We investigated the immunological characteristics of human nocardiosis and examined the component cells of the granulomatous lesions. A 66-year-old man with diffuse large B-cell lymphoma presented with fever and multiple nodules in the lung during chemotherapy. The blood culture formed white colonies, but their characterization was difficult by routine microbiological laboratory methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry identified the colonies as . Meanwhile, the patient suddenly experienced an epileptic seizure without a brain abscess. His cerebrospinal fluid (CSF) showed neutrophilic pleocytosis (108/mm). The conventional agar culturing failed to isolate colonies, but culturing with brain-heart infusion agar generated colonies. These colonies were completely concordant with those from the blood, as confirmed by 16S rRNA gene sequencing. Therefore, the patient had developed meningitis through sepsis induced by . His CD4-positive T-lymphocyte counts were low, and oligoclonal CD8-positive αβ T-lymphocytes were present in the blood prior to the first and after three cycles of chemotherapy. He had bone marrow granulomatous lesions comprising lymphoma and CD8-positive αβ T-cells. Treatment with sulfamethoxazole/trimethoprim relieved all of his symptoms. The combined analysis by microbiological and molecular methods determined the cause of his epileptic seizure. His immunological characteristics, including low CD4-positive or CD8-positive αβ T-lymphocytes, may have contributed to the unusual clinical presentations by , which rarely involves the central nervous system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957946PMC
January 2018

Prognostic Factors for the Survival of Elderly Patients Who Were Hospitalized in the Medical Ward of Our Hospital in Japan.

Authors:
Shuichi Abe

Geriatrics (Basel) 2017 Nov 2;2(4). Epub 2017 Nov 2.

Internal Medicine, Rehabilitation Oomiko Hospital, Oomiko19, Oohara-cho, Tokushima-City, Tokushima 770-8012, Japan.

It has been a long time since there were many elderly people in Japan. The medical care and costs for the elderly are enormous, and research to lower the mortality rate of the elderly is needed. We retrospectively investigated the prognostic factors for the survival of elderly patients who were hospitalized in the medical ward of our hospital. In total, 277 patients who were hospitalized between 1 January 2014 and 31 May 2017, were included in the retrospective study. Univariate and multivariate analyses of items (vital signs, laboratory data, and so on) were performed, and significant differences between the survival group and death group were subjected to receiver operating characteristic curve analysis. Serum urea nitrogen levels and serum albumin levels provided a relatively high area under the curve (AUC). However, there was no item for which AUC exceeded 0.70, and setting the cutoff value in this study was difficult. For treating the elderly, it is important to carefully evaluate each patient's prognostic factors, including the demented state, renal function, and nutritional state; personalized treatment of each patient is also important.
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http://dx.doi.org/10.3390/geriatrics2040032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371180PMC
November 2017

MafB enhances efferocytosis in RAW264.7 macrophages by regulating Axl expression.

Immunobiology 2018 01 6;223(1):94-100. Epub 2017 Oct 6.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.

The transcription factor MafB is involved in cellular differentiation and phagocytosis in macrophages. Macrophages phagocytose apoptotic cells in vivo; this process, which is known as efferocytosis, requires Axl receptor tyrosine kinase (Axl) activity. However, the association between MafB and efferocytosis, as well as that between MafB and Axl, in macrophages is unknown. We hypothesized that MafB modulates macrophage efferocytosis by regulating Axl expression. Fluorescent-labeled apoptotic thymocytes were added to RAW264.7-MafB-shRNA and control cells, and the proportion of phagocytosis-positivey fluorescence microscopy and flow cytometry. In addition, Axl mRNA and protein were quantified by real-time PCR and western blotting in each group. RAW264.7-MafB-shRNA cells were transfected with a plasmid expressing green fluorescent protein (GFP)-tagged Axl or a control empty plasmid expressing only GFP. The capacity for phagocytosis of apoptotic cells was assessed in GFP-positive cells gated based on fluorescence intensity. In RAW264.7-MafB-shRNA cells, capacity for phagocytosis of apoptotic thymocytes was significantly reduced compared with that of control cells, as determined by fluorescence microscope and flow cytometry. Axl mRNA and protein expression was significantly reduced in RAW264.7-MafB-shRNA cells relative to control cells. Furthermore, the capacity of RAW264.7-MafB-shRNA cells, transfected with an Axl-expressing plasmid, for phagocytosis of apoptotic thymocytes was significantly greater than that of cells transfected with the control plasmid. Collectively, the present findings indicate that MafB enhances efferocytosis by regulating Axl expression in RAW264.7 macrophages.
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http://dx.doi.org/10.1016/j.imbio.2017.10.007DOI Listing
January 2018

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity.

Respir Res 2017 09 15;18(1):172. Epub 2017 Sep 15.

Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Background: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear.

Methods: Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin.

Results: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects.

Conclusions: These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function.
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http://dx.doi.org/10.1186/s12931-017-0654-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603061PMC
September 2017

MafB silencing in macrophages does not influence the initiation and growth of lung cancer induced by urethane.

EXCLI J 2017 20;16:914-920. Epub 2017 Jun 20.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.

An increased number of tumor-associated macrophages (TAMs) that exhibit the M2 macrophage phenotype is related to poorer prognosis in cancer patients. MafB is a transcription factor regulating the differentiation of macrophages. However, involvement of MafB for the development of TAMs is unknown. This study was designed to investigate the role of MafB in a murine urethane-induced lung cancer model. Urethane was injected intraperitoneally into wild-type and dominant-negative MafB transgenic mice. Twenty-four weeks later, mice were sacrificed and their lungs removed for pathological analysis. The numbers and mean areas of lung cancer were evaluated. In addition, the numbers of Mac-3-positive macrophages were evaluated in each tumor. The numbers and mean areas of lung cancer induced by urethane administration were not significantly different between wild-type and dominant-negative MafB transgenic mice. The numbers of TAMs in lung cancer tissue were not significantly different between the two groups. MafB silencing using dominant-negative MafB did not influence the initiation and growth of lung cancer in mice exposed to urethane. These data suggest that MafB may not be related to the development of TAMs.
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http://dx.doi.org/10.17179/excli2017-325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579402PMC
June 2017

A case of ceftriaxone-associated biliary pseudolithiasis in an elderly patient with renal dysfunction.

Authors:
Shuichi Abe

IDCases 2017 27;9:62-64. Epub 2017 Jun 27.

Rehabilitation Oomiko Hospital, Internal Medicine. Oomiko19, Oohara-cho, Tokushima-city, Tokushima, 770-8012, Japan.

Prior literature suggests that ceftriaxone causes formation of gallbladder stones at a relatively high frequency, and when abdominal symptoms occur, prompt investigation of the gallbladder is required with institution of appropriate treatment. Aging, malnutrition, renal impairment, and sepsis are risk factors for pseudolithiasis, and prevention of these is important to suppress gallstone development.
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http://dx.doi.org/10.1016/j.idcr.2017.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499111PMC
June 2017

MafB enhances the phagocytic activity of RAW264.7 macrophages by promoting Fcgr3 expression.

Biochem Biophys Res Commun 2017 Jan 12;482(2):375-381. Epub 2016 Nov 12.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.

This study was designed to investigate whether MafB influences the phagocytic activity of macrophages by modulating the expression of the Fc receptors for IgG (FcγRs), Fcgr2b and Fcgr3. In macrophages, FcγRs are critical for the phagocytosis of opsonized pathogens. Of these receptors, Fcgr3 has been shown to play an important role in host defense. As a model to evaluate the mechanism by which MafB influences phagocytosis, we utilized a macrophage cell-line that constitutively expresses a MafB-specific short hairpin (sh)RNA (RAW264.7-MafB-shRNA). Specifically, the levels of Fc receptor mediated-phagocytosis and the levels of FcγRs surface expression were evaluated by flow cytometry analysis, while quantitative real-time PCR analysis was utilized to examine the mRNA expression levels of FcγRs. Compared to the control cell population, RAW264.7-MafB-shRNA cells exhibited significant reductions in Fcgr3 expression and Fc receptor-mediated phagocytosis, but no difference in Fcgr2b expression. Likewise, there was markedly decreased surface expression of Fcgr3 antigen, but not Fcgr2b antigen, in RAW264.7-MafB-shRNA, compared to the control cells. Meanwhile, the observed reduction in the phagocytic activity of the MafB-shRNA-expressing cells was attenuated by ectopic expression of Fcgr3. Together, the results presented here indicate that MafB influences the phagocytic activity of macrophages by promoting Fcgr3, but not Fcgr2b, expression.
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http://dx.doi.org/10.1016/j.bbrc.2016.11.070DOI Listing
January 2017

Role of chemokine C-C motif ligand-1 in acute and chronic pulmonary inflammations.

Springerplus 2016 2;5(1):1241. Epub 2016 Aug 2.

Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.

Background: Chemokine C-C motif ligand 1 (CCL1) accumulates C-C motif chemokine receptor 8 positive leukocytes to the inflammatory sites. Single-nucleotide polymorphisms in the chemokine CCL1 gene are associated with exacerbation of chronic obstructive lung disease. However, it is unclear whether CCL1 has immunomodulatory functions during pulmonary inflammation. This study aimed to elucidate this issue using newly generated transgenic mice that express CCL1 in the lungs (SPC-CCL1 mice).

Methods: To evaluate the phenotypes of these mice, lung section and bronchoalveolar lavage (BAL) fluid analyses were performed. We intratracheally administered lipopolysaccharide (LPS) or Mycobacterium bovis as a model of acute or chronic lung inflammation, respectively.

Results: No histological differences were observed between lung tissue from SPC-CCL1 Tg and wild-type mice in the resting condition and after LPS administration. In the resting condition, the total BAL cell concentration was lower in SPC-CCL1 Tg mice than in wild-type mice (P = 0.0097). Flow cytometric analyses showed that SPC-CCL1 Tg mice had fewer F4/80-positive cells than wild-type mice (P = 0.0278). After intratracheal LPS administration, CCL1 overexpression changed neither the total numbers nor population of BAL cells. After mycobacterial administration, pulmonary granuloma formation was significantly enhanced. The degree of Immunostaining for endoplasmic reticulum to nucleus signaling 1, a molecule associated with granuloma formation and endoplasmic reticulum stress, was significantly enhanced in the granuloma regions of SPC-CCL1 mice treated with Mycobacterium, compared to those of wild-type mice.

Conclusions: CCL1 overexpression in the lungs did not change the acute inflammatory response induced by LPS, but enhanced granuloma formation after mycobacterial treatment, possibly through enhancing endoplasmic reticulum stress.
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http://dx.doi.org/10.1186/s40064-016-2904-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970990PMC
August 2016

[Risk Factor Analysis of Pneumonia after Cardiovascular Surgery].

Kyobu Geka 2016 Aug;69(9):731-8

Second Department of Surgery, Yamagata University, Yamagata, Japan.

Pneumonia is a major and life-threatening complication after cardiovascular surgery. The objective of our study was to describe epidemiology, clinical characteristics, and risk factors of pneumonia after cardiovascular surgery. From January 2007 to December 2011, 511 consecutive patients (age 67.3±11.9;336 men, 175 women) were enrolled in this study. Pneumonia was diagnosed according to Centers of Disease Control and Prevention surveillance criteria for healthcare associated infection. Data collection included preoperative, intraoperative, and post-operative variables. The overall incidence of pneumonia was 72 cases(14.0%). The mortality in pneumonia group was significantly higher than that in non-pneumonia group (16.6% vs 4.3%, Odds ratio 4.4 p<0.001). Multi-logistic analysis revealed that elderly patient, preoperative congestive heart failure, preoperative hemodialysis, and operation of the thoracic aorta were independent risk factors for pneumonia after cardiovascular surgery.
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August 2016

The role of macrophage transcription factor MafB in atherosclerotic plaque stability.

Atherosclerosis 2016 07 14;250:133-43. Epub 2016 May 14.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan.

Background And Aims: Macrophage differentiation is associated with the development of atherosclerosis and plaque vulnerability and is regulated by transcription factor MafB. We previously reported that MafB attenuates macrophage apoptosis, which is associated with atherosclerotic plaque instability. The aim of this study was to elucidate the role of MafB in the progression of atherosclerotic plaque.

Methods: We generated macrophage-specific dominant-negative (DN) MafB transgenic mice and intercrossed DN-MafB mice with apolipoprotein E (ApoE) knockout (KO) mice.

Results: There was no significant difference in advanced atherosclerotic lesion area between DN-MafB/ApoE KO mice and littermate control ApoE KO mice 9 weeks after high-cholesterol diet. However, DN-MafB/ApoE KO mice showed significantly larger necrotic cores and lower collagen content in atherosclerotic plaques than ApoE KO mice. Although there was no difference in intraplaque macrophage infiltration and efferocytosis, DN-MafB/ApoE KO mice showed significantly more apoptotic macrophages at the plaque edges than did ApoE KO mice. Real-time PCR analysis revealed that peritoneal macrophages of DN-MafB/ApoE KO mice had a greater increase in matrix metalloproteinase-9 and mRNA expression of inflammatory/M1 macrophage markers (tissue necrosis factor-α, interleukin-6, CD11c, and p47phox) after lipopolysaccharide stimulation than those of ApoE KO mice.

Conclusion: Macrophage-specific inhibition of MafB may destabilize atherosclerotic plaques in advanced lesions.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.05.021DOI Listing
July 2016

Promising biological therapies for ulcerative colitis: A review of the literature.

World J Gastrointest Pathophysiol 2015 Nov;6(4):219-27

Hirotada Akiho, Azusa Yokoyama, Shuichi Abe, Yuichi Nakazono, Masatoshi Murakami, Yoshihiro Otsuka, Kyoko Fukawa, Mitsuru Esaki, Yusuke Niina, Haruei Ogino, Department of Gastroenterology, Kitakyushu Municipal Medical Center, Fukuoka 802-0077, Japan.

Ulcerative colitis (UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants (including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab (anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab (another anti-TNF-α agent), tofacitinib (a Janus kinase inhibitor), and vedolizumab and etrolizumab (integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.
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http://dx.doi.org/10.4291/wjgp.v6.i4.219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644886PMC
November 2015

Low arterial blood oxygenation is associated with calcification of the coronary arteries in patients with chronic obstructive pulmonary disease.

Respir Investig 2015 May 21;53(3):111-6. Epub 2015 Feb 21.

Yamagata University School of Medicine, Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan. Electronic address:

Background: Cigarette smoking is a well-known major cause of both chronic obstructive pulmonary disease (COPD) and atherosclerosis. However, few studies have investigated the correlation between COPD and coronary atherosclerosis.

Methods: We recruited 54 patients with stable COPD (51 men, 3 women) but without angina symptoms. Arterial blood gas analyses were performed, pulmonary function was assessed, and calcification of the coronary arteries was evaluated by computed tomography (CT).

Results: Calcification of the coronary arteries was noted in 25 patients. There were no significant differences in age, body mass index, respiratory function, and levels of low-density lipoprotein cholesterol, hemoglobin A1c, glucose, or C-reactive protein between patients with or without calcification of the coronary arteries. Arterial blood oxygenation was significantly lower in patients with calcification of the coronary arteries. On both univariate and multivariate analyses, low arterial blood oxygenation was an independent risk factor for calcification of the coronary arteries.

Conclusions: In patients with COPD, low arterial blood oxygenation was strongly associated with calcification of the coronary arteries and may be a significant predictor of cardiovascular disease.
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http://dx.doi.org/10.1016/j.resinv.2015.01.002DOI Listing
May 2015

[Clinical characteristics of biliary tract infection and acalculous cholecystitis after cardiovascular surgery].

Kyobu Geka 2014 Nov;67(12):1039-43; discussion 1043-6

Second Department of Surgery, Yamagata University Hospital, Yamagata, Japan.

Biliary tract infection (BTI) including acalculous cholecystitis is a rare but life-threatening complication after cardiovascular surgery. The objective of our study was to describe epidemiology, clinical characteristics, and risk factors of BTI after cardiovascular surgery. From January 2007 to December 2011, 586 consecutive patients(age68±11;397 men,189 women)were enrolled in this study. BTI was diagnosed according to Centers for Disease Control and Prevention (CDC) surveillance criteria for healthcare associated infection. Data collection included preoperative, intraoperative, and post-operative variables. The overall incidence of BTI was 3.9%. The mortality in BTI group was significantly higher than that in non-BTI group (17.1% vs 5.5%, p<0.05). Multi-logistic analysis revealed that operation of the thoracic aorta( p<0.05) and massive transfusion(p<0.01) were independent risk factors for BTI after cardiovascular surgery.
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November 2014

Pulmonary macrophage transplantation therapy.

Nature 2014 Oct 1;514(7523):450-4. Epub 2014 Oct 1.

1] Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [2] Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [3] Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.

Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-β-deficient (Csf2rb(-/-)) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.
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http://dx.doi.org/10.1038/nature13807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236859PMC
October 2014

Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

Int J Biol Sci 2014 13;10(8):882-94. Epub 2014 Aug 13.

Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.
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http://dx.doi.org/10.7150/ijbs.8737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147222PMC
March 2015

[Procalcitonin as a marker of the postoperative infection in cardiovascular surgery].

Kyobu Geka 2014 Jul;67(7):519-23; discussion 523-5

Second Department of Surgery, Yamagata University, Yamagata, Japan.

Background: Procalcitonin( PCT) is a new diagnostic marker of severe bacterial infection and sepsis.

Purpose: To evaluate the usefulness of PCT in patients with suspicion of bacterial infection after cardiovascular surgery.

Methods: From January 2012 to December 2012, 150 consecutive patients after cardiovascular surgery were studied retrospectively. Postoperative infection was diagnosed under Centers for Disease Control and Prevention (CDC) guideline for healthcare associated infection, and biomarker levels and microbiological specimen were evaluated.

Results: Only blood stream infection group revealed higher PCT levels( median 5.0 ng/ml) than non blood stream infection group( median 0.1 ng/ml)[p<0.01].

Conclusion: PCT is the best biomarker available for the clinical diagnosis of blood stream infection after cardiovascular surgery.
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July 2014

Association between plasma adiponectin levels and decline in forced expiratory volume in 1 s in a general Japanese population: the Takahata study.

Int J Med Sci 2014 21;11(8):758-64. Epub 2014 May 21.

1. Department of Cardiology, Pulmonology, and Nephrology;

Background: Adiponectin is an anti-inflammatory and cardio-protective cytokine. However, several studies have demonstrated that plasma adiponectin levels were inversely associated with pulmonary function in patients with chronic obstructive pulmonary disease, suggesting a proinflammatory or pulmonary-destructive role. It is still unclear whether adiponectin is a potent biomarker predicting declines in pulmonary function. The aim of this study was to investigate the association between adiponectin and pulmonary function among Japanese individuals who participated in an annual health check-up.

Methods: Spirometry and blood sampling, including measurements of plasma adiponectin, were performed for 3,253 subjects aged 40 years or older who participated in a community-based annual health check-up in Takahata, Japan from 2004 to 2006. In 2011, spirometry was re-performed, and the data from 872 subjects (405 men and 467 women) were available for a longitudinal analysis.

Results: Plasma adiponectin levels were found to be significantly associated with age, body mass index (BMI), and alanine aminotransferase (ALT), triglycerides (TG), and high-density lipoprotein-cholesterol (HDL-c) levels among both men and women in the study population. Plasma adiponectin levels were found to be associated with lifetime cigarette consumption (Brinkman index, BI) in men only. Plasma adiponectin levels were inversely correlated with forced expiratory volume in 1 s (FEV1) per forced vital capacity in both men and women. In addition, the annual change in FEV1 was inversely associated with plasma adiponectin levels in both genders. A multiple linear regression analysis revealed that this association was independent of other confounding factors such as age, BMI, BI, ALT, TG, and HDL-c.

Conclusions: The results of the present study suggest that adiponectin levels are predictive of declines in FEV1 in the general population.
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http://dx.doi.org/10.7150/ijms.8919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057484PMC
February 2015

Relationship between Serum Level of Lymphatic Vessel Endothelial Hyaluronan Receptor-1 and Prognosis in Patients with Lung Cancer.

J Cancer 2014 11;5(3):242-7. Epub 2014 Mar 11.

Department of Cardiology, Pulmonology, and Nephrology,Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

Background: Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) is a hyaluronic acid receptor that is selectively expressed in the endothelia of lymphatic capillaries. The density of lymphatic vessels expressing LYVE-1 on immunohistochemistry negatively correlates with prognosis of patients with non-small-cell lung cancer. However, the relationship between LYVE-1 serum levels and lung cancer staging is unknown.

Methods: We collected blood samples from 58 lung cancer patients before treatment and measured LYVE-1 serum levels using an enzyme-linked immunosorbent assay.

Results: Mean serum LYVE-1 levels were 1,420 pg/mL. Serum LYVE-1 levels correlated positively with serum albumin levels, but inversely with primary tumor size, leukocyte counts, and platelet counts by Pearson's product-moment correlation coefficient. A high cancer staging, occurrence of lymph-node metastases, and occurrence of distant metastases were significantly associated with low LYVE-1 levels. Moreover, multiple logistic regression analyses revealed that LYVE-1 levels were predictive of the presence of lymph node and distant metastases, independently of the other factors. Kaplan-Meier analysis showed that the survival of patients with serum LYVE-1 ≤1,553 pg/mL was significantly poorer than that of patients with serum LYVE-1 >1,553 pg/mL. This survival difference relative to LYVE-1 levels remained statistically significant after adjusting for age and gender by the Cox proportional-hazard analysis.

Conclusion: Serum LYVE-1 is significantly low in lung cancer patients with metastasis, compared with those without. Measuring LYVE-1 levels in lung cancer patients may be useful for evaluating lung cancer progression.
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http://dx.doi.org/10.7150/jca.8486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963081PMC
March 2014