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  • 1
    In: Digestion, S. Karger AG, Vol. 101, No. 5 ( 2020), p. 579-589
    Abstract: Background/Aims: Recently, postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) has attracted attention. However, the criteria for computed tomography (CT) scanning following esophageal endoscopic submucosal dissection (ESD) are unclear. In this study, we aimed to identify the predictive factors of PEECS and the usefulness of CT scanning after esophageal ESD. Methods: A total of 245 lesions in 223 patients who underwent esophageal ESD between February 2008 and October 2018 were retrospectively analyzed. Patients with double cancers, those who experienced procedural accidents, such as aspiration pneumonitis or perforation, and those who were unable to undergo CT were excluded from the study. PEECS evaluation items included body temperature (≤37.7°C = 1 point, ≥37.8°C = 2 points), white blood cell count ( 〈 10,800/μL = 1 point, ≥10,800/μL = 2 points), and chest pain (numerical rating scale [NRS] ≤4 = 1 point, NRS ≥5 = 2 points). Scores of ≥5 points were categorized as the PEECS-positive group, and scores of ≤4 points were categorized as the PEECS-negative group. The degree of mediastinal emphysema on CT was stratified into 5 grades, in which grades 0 and 1 were considered as the “low-grade” group, and grades 2, 3, and 4 were considered as the “high-grade” group. We analyzed the prognostic factors of high-grade mediastinal emphysema, including the presence or absence of PEECS. Results: The PEECS-positive group comprised 18 out of the 163 patients (11.0%), and mediastinal emphysema was stratified into grades 0 (94), 1 (51), 2 (12), 3 (5), and 4 (1 patient). Three independent risk factors for the onset of PEECS were identified, as follows: resected area ≥750 mm2 (OR 7.28, 95% CI 1.42–37.33, p = 0.017), treatment duration ≥75 min (OR 10.26, 95% CI 1.20–87.77, p = 0.034), and muscle layer exposure (OR 10.92, 95% CI 2.22–53.74, p = 0.003). Two independent predictive factors of high-grade mediastinal emphysema were identified, which were PEECS positivity (OR 4.31, 95% CI 1.29–14.41, p = 0.018), and muscle layer exposure (OR 4.08, 95% CI 1.18–14.06, p = 0.026). Conclusions: A large resected area, prolonged treatment duration, and muscle layer exposure are risk factors for the onset of PEECS. Mediastinal emphysema was observed in 43% of patients following ESD. When marked clinical symptoms of PEECS appear, high-grade mediastinal emphysema may be observed, and therefore CT should be performed in these cases.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
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  • 2
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 178, No. 4 ( 2019), p. 355-362
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. 〈 b 〉 〈 i 〉 Method: 〈 /i 〉 〈 /b 〉 This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included 〈 i 〉 Moraxella catarrhalis 〈 /i 〉 ( 〈 i 〉 n 〈 /i 〉 = 6) and 〈 i 〉 Klebsiella pneumoniae 〈 /i 〉 ( 〈 i 〉 n 〈 /i 〉 = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
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  • 3
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 185, No. 8 ( 2024), p. 729-738
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 The muscarinic M3 receptor antagonist, tiotropium, has a bronchodilatory effect on asthma patients. Additionally, tiotropium inhibits allergic airway inflammation and remodeling in a murine asthma model. However, the underlying mechanisms of this M3 receptor antagonist remain unclear. Therefore, we investigated the effect of muscarinic M3 receptor blockage on M2 macrophage development during allergic airway inflammation. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 BALB/c mice were sensitized and challenged with ovalbumin to develop a murine model of allergic airway inflammation mimicking human atopic asthma. During the challenge phase, mice were treated with or without tiotropium. Lung cells were isolated 24 h after the last treatment and gated using CD68-positive cells. Relm-α and Arginase-1 (Arg1) (M2 macrophage markers) expression was determined by flow cytometry. Mouse bone marrow mononuclear cell-derived macrophages (mBMMacs) and human peripheral blood mononuclear cells (PBMCs)-derived macrophages were stimulated with IL-4 and treated with a muscarinic M3 receptor antagonist 〈 i 〉 in vitro 〈 /i 〉 . 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The total cells, eosinophils, and IL-5 and IL-13 levels in BAL fluids were markedly decreased in the asthma group treated with tiotropium compared to that in the untreated asthma group. The Relm-α and Arg1 expression in macrophages was reduced considerably in the asthma group treated with tiotropium compared to that in the untreated asthma group, suggesting that the development of M2 macrophages was inhibited by muscarinic M3 receptor blockage. Additionally, muscarinic M3 receptor blockage 〈 i 〉 in vitro 〈 /i 〉 significantly inhibited M2 macrophage development in both mBMMacs- and PBMCs-derived macrophages. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Muscarinic M3 receptor blockage inhibits M2 macrophage development and prevents allergic airway inflammation. Moreover, muscarinic M3 receptors might be involved in the differentiation of immature macrophages into M2 macrophages.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2024
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  • 4
    In: Oncology, S. Karger AG, Vol. 70, No. 6 ( 2006), p. 465-473
    Abstract: Various imaging methods have been employed for the extracorporeal detection of malignant tumors in the human body, such as scintigraphy and PET; however, none is sufficiently accurate and all are also very expensive. To resolve these issues, we attempted to develop a new imaging technique of photodynamic diagnosis (PDD) with acridine orange (AO). AO has the ability to rapidly and specifically accumulate in malignant tumors and emit brilliant green fluorescence after blue light excitation. In this study, we investigated the feasibility of PDD utilizing the fluorovisualization effect of AO, for the extracorporeal detection of mouse osteosarcoma inoculated into the soft tissues. At 2 h after intravenous administration of 0.1, 0.2, 0.5, 1.0, 2.0 and 5.0 mg/kg AO, the tumor and the surrounding normal tissues were illuminated by blue light. The visual fluorescence contrast and ratio (X) of the difference in fluorescence intensity between the tumor and the surrounding normal tissues were evaluated using a high-resolution digital camera equipped with an absorption filter. In addition, the fluorescence contrast was also detected sequentially at 0.5, 1, 2, 3, 6 and 12 h after intravenous administration of AO at 1.0 mg/kg. The results revealed that the optimal condition for clear detection of the tumor was evaluation 2 h after intravenous injection of AO at 0.1 mg/kg, because it provided the best visual contrast on the digital images, and the fluorescence intensity as well as the value of X were higher as compared to the values under other conditions of dose and timing. Based on the results of an acute toxicity study of AO, the estimated LD 〈 sub 〉 50 〈 /sub 〉 of this substance following intravenous administration was 27.30 mg/kg. In conclusion, we believe that PDD using AO administered intravenously may be feasible for the detection of human musculoskeletal sarcomas in the soft tissues at extremities, and this technique might be a less invasive, less expensive, quicker and more accurate imaging modality than other previously reported imaging methods for this purpose.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1483096-6
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  • 5
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 113, No. 1-3 ( 1997), p. 323-325
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1997
    detail.hit.zdb_id: 1108932-5
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  • 6
    In: Digestion, S. Karger AG, Vol. 104, No. 2 ( 2023), p. 97-108
    Abstract: Introduction: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. Methods: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. Results: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865–0.965, p 〈 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797–0.973, p 〈 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. Conclusion: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1482218-0
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  • 7
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 168, No. 3 ( 2015), p. 165-172
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against 〈 i 〉 Dermatophagoides pteronyssinus 〈 /i 〉 , crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), 〈 i 〉 Candida 〈 /i 〉 (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
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    detail.hit.zdb_id: 1482722-0
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  • 8
    In: Pharmacology, S. Karger AG, Vol. 59, No. 4 ( 1999), p. 171-182
    Abstract: The occupancy of 1,4-dihydropyridine (DHP) receptors by pranidipine was characterized in tissues of spontaneously hypertensive rats (SHR). Oral administration of pranidipine (1 and 3 mg/kg) in SHR produced significant (26–67%) decreases in the number of specific (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding sites (B 〈 sub 〉 max 〈 /sub 〉 ) with 2- to 4-fold increases in the apparent dissociation constant (K 〈 sub 〉 d 〈 /sub 〉 ) in myocardial tissues at 1, 3 and 6 h later. In these rats, there was a reduction (16–37%) of B 〈 sub 〉 max 〈 /sub 〉 in cerebral cortical (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding. Occupancy of myocardial DHP receptors after oral administration of pranidipine correlated well with its plasma concentration. Oral administration of nifedipine (10 mg/kg) in SHR caused significant increase in K 〈 sub 〉 d 〈 /sub 〉 values for (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding in myocardium and cerebral cortex at 1 h later. In vivo specific (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding in particulate fractions of SHR aorta was markedly (59–78%) reduced at 1, 3 and 12 h after oral administration of pranidipine (3 mg/kg), while myocardial (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding was decreased by 46–48% at 1 and 3 h later. In these rats, there was a significant decrease (34%) in cerebral cortical (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding at 3 h later. In contrast, nifedipine administration produced a similar degree of reduction (71–84%) of in vivo (+)-[ 〈 sup 〉 3 〈 /sup 〉 H]PN 200-110 binding in the myocardium, aorta and cerebral cortex. It is concluded that pranidipine may exert more selective and sustained occupation in vivo of DHP receptors in vascular tissues of SHR than in myocardial and brain tissues.
    Type of Medium: Online Resource
    ISSN: 0031-7012 , 1423-0313
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1999
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    detail.hit.zdb_id: 1483550-2
    SSG: 15,3
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  • 9
    In: Oncology, S. Karger AG, Vol. 67, No. 2 ( 2004), p. 166-173
    Abstract: It is well known that malignant cells show procoagulant activity, which is associated with their metastatic potential. Thrombin, the key enzyme of the blood coagulation system, is generated around tumor cells, promoting the migration and metastasis of tumor cells. In this study, we evaluated the effect of argatroban, a specific thrombin inhibitor, on the migration and metastasis of B16BL6 melanoma cells. In vitro argatroban dose-dependently inhibited cell migration, the maximum inhibition being observed in the presence of 10 µ 〈 i 〉 M 〈 /i 〉 argatroban (p 〈 0.0001). In order to investigate the antimetastatic effect of the thrombin inhibitor, we used an animal model that we have reported previously. C57BL6 mice which had received a bone (femur or tibia) transplanted into the dorsal subcutis were injected with B16 melanoma cells into the left heart ventricle. Intraperitoneal injection of argatroban (9 mg/kg/day for 4 weeks) significantly reduced the number of limbs with metastatic lesions as compared to a placebo (p 〈 0.05). These results suggest that argatroban was associated with reduced melanoma metastases by inhibiting cell migration. Our results showed that argatroban is effective for treatment of bone metastasis.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 10
    In: Oncology, S. Karger AG, Vol. 77, No. 2 ( 2009), p. 92-99
    Abstract: Decorin, the prototype of an expanding family of small leucine-rich proteoglycans, is involved in a number of cellular processes including matrix assembly, fibrillogenesis and the control of cell proliferation. In this study, we investigated the role of decorin in suppressing tumor aggressiveness and bone metastases. We used a metastatic breast cancer cell line, MDA-MB-231, to show that decorin causes marked growth suppression bothin vitro and in vivo. A cytomegaloviral vector containing the decorin transgene caused greatly reduced cell growth, motility and observed metastases. Bone metastases were decreased by 〉 90% upon decorin transfection. These results demonstrate a novel role for decorin in the reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapies for metastatic breast cancer.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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