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  • 1
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    A Possible Role of TARC in Antigen-Specific Th2-Dominant Responses in Patients with Paragonimiasis westermani
    S. Karger AG ; 2004
    In:  International Archives of Allergy and Immunology Vol. 134, No. 3 ( 2004), p. 248-252
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 134, No. 3 ( 2004), p. 248-252
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Paragonimiasis westermani (Pw), a common parasitic zoonosis in Asia, is typically associated with eosinophilia. Th2 cytokines seem to have an important role in the clinical manifestations of this disease. Thymus and activation-regulated chemokine (TARC) is a potential key regulator of Th2-mediated inflammation. The purpose of the present study was to evaluate the antigen-specific Th2-dominant responses in patients with Pw. 〈 i 〉 Methods: 〈 /i 〉 The concentrations of cytokines and chemokines in supernatants of peripheral blood mononuclear cell (PBMC) cultures with or without antigen stimulation were measured by enzyme-linked immunosorbent assay (ELISA). TARC levels in serum from Pw patients were also evaluated by ELISA. The number of Th2 cells expressing the CC-chemokine receptor 4 (CCR4) in the peripheral blood was evaluated by flow cytometry. 〈 i 〉 Results: 〈 /i 〉 Antigen-stimulation induced production of IL-5 and IL-13, but not IFN-γ from PBMC cultures in patients with Pw. Pw patients had elevated serum TARC levels and a higher proportion of CCR4-expressing cells among CD4+ T cells in the peripheral blood. There were also higher levels of TARC, but not IP-10, in supernatants of antigen-stimulated PBMC culture compared to unstimulated PBMC culture in patients with Pw. 〈 i 〉 Conclusion: 〈 /i 〉 Our findings clarify antigen-specific Th2-dominant responses in patients with Pw and suggest a possible role for TARC in Th2-dominant responses.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000078773
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 1482722-0
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  • 2
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    Accumulation of CXCR3-Expressing Eosinophils and Increased Concentration of Its Ligands (IP10 and Mig) in Bronchoalveolar Lavage Fluid of Patients with Chronic Eosinophilic Pneumonia
    S. Karger AG ; 2005
    In:  International Archives of Allergy and Immunology Vol. 137, No. 3 ( 2005), p. 229-235
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 137, No. 3 ( 2005), p. 229-235
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Since human peripheral eosinophils have been shown to migrate to the CXC chemokine receptor 3 (CXCR3) ligands IFN-γ-inducible protein 10 (IP10) and monokine induced by IFN-γ (Mig), this confirms that CXCR3 is functionally expressed on these cells. IP10 expression has been shown to be increased in the airways of asthmatics. Eosinophil accumulations are found in bronchoalveolar lavage fluid (BALF) from patients with chronic eosinophilic pneumonia (CEP). To examine the contribution of IP10 and Mig in the pathogenesis of CEP, we measured the concentration of IP10 and Mig, and evaluated the expression of CXCR3 on eosinophils in BALF taken from patients with CEP. 〈 i 〉 Methods: 〈 /i 〉 The concentrations of IP10 and Mig in BALF were measured by ELISA. The proportion of CXCR3-expressing CD4+ T cells and CD16-negative eosinophils was determined by flow cytometry. 〈 i 〉 Results: 〈 /i 〉 The BALF concentrations of IP10 and Mig were higher in patients with CEP, as well as in patients with sarcoidosis, when compared to healthy controls. The absolute number of CXCR3+ CD4+ T cells was significantly higher in the BALF of patients with sarcoidosis, but not in the patients with CEP, when compared to healthy volunteers. There were higher percentages of CXCR3-expressing eosinophils in the BALF than in the peripheral blood of patients with CEP. 〈 i 〉 Conclusions: 〈 /i 〉 Our findings suggest that IP10 and Mig contribute to the accumulation of CXCR3-expressing eosinophils in the lungs of patients with CEP, and modulate the eosinophilic inflammation of the lung.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000086335
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2005
    detail.hit.zdb_id: 1482722-0
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  • 3
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    Involvement of Galectin-9 in Lung Eosinophilia in Patients with Eosinophilic Pneumonia
    S. Karger AG ; 2010
    In:  International Archives of Allergy and Immunology Vol. 153, No. 3 ( 2010), p. 294-302
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 153, No. 3 ( 2010), p. 294-302
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Although we first found galectin-9 (Gal-9) as an eosinophil chemoattractant, its role in eosinophilic inflammation is still obscure. The purpose of the present study is to clarify the role of Gal-9 in human eosinophilic pulmonary inflammation in comparison with eotaxin (CCL11). 〈 i 〉 Methods: 〈 /i 〉 We measured the levels of Gal-9 and eotaxin in the bronchoalveolar lavage fluid (BALF) of patients with acute and chronic eosinophilic pneumonia (AEP and CEP). Furthermore, the biological activities (chemotaxis and apoptosis) of Gal-9 were compared with those of eotaxin using interleukin-5-primed or -unprimed eosinophils. 〈 i 〉 Results: 〈 /i 〉 The levels of Gal-9 and eotaxin in the BALF from patients with AEP and those with CEP were higher than those found in the controls. Although there was little difference in Gal-9 level between patients with AEP and patients with CEP, the eotaxin level was significantly lower in patients with CEP. In patients with AEP, the eosinophil number correlated well with both the Gal-9 and eotaxin levels. However, in patients with CEP, the eosinophil number only correlated well with the Gal-9 level. Moreover, the Gal-9 level correlated with the eotaxin level in patients with AEP, but there was no significant correlation between those levels in patients with CEP. Anti-Gal-9 antibody treatment strongly reduces eosinophil chemotactic activity in the BALF of patients with AEP and in that of patients with CEP, whereas the anti-CCR3 (receptor for eotaxin) antibody strongly reduces this activity in the BALF of patients with AEP but not in that of patients with CEP. Furthermore, Gal-9 exhibited both chemotactic and proapoptotic activities for activated eosinophils, though eotaxin only exhibited chemotactic activity. 〈 i 〉 Conclusions: 〈 /i 〉 The present results provide two possibilities: that Gal-9 is involved in pulmonary eosinophilia in patients with AEP and CEP, and that Gal-9 exhibits regulatory functions for activated eosinophils at the site of inflammation.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000314371
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2010
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  • 4
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    Preclinical Cushing’s Syndrome Resulting from Black Adrenal Adenoma
    S. Karger AG ; 2004
    In:  Hormone Research in Paediatrics Vol. 62, No. 2 ( 2004), p. 60-66
    Details
    In: Hormone Research in Paediatrics, S. Karger AG, Vol. 62, No. 2 ( 2004), p. 60-66
    Abstract: A 59-year-old Japanese woman, admitted for the treatment of diabetes mellitus and hypertension, was incidentally discovered to have a solid mass of 1.4 cm in diameter by CT scan with the attenuation value of 38 Hounsfield units, relatively higher for ordinary adrenal adenomas. Magnetic resonance imaging revealed no reduction of signal intensity on opposite-phase image on T1-weighted sequence. Adrenal scintigraphy imaging with 〈 sup 〉 131 〈 /sup 〉 I-adosterol did not show any uptake of the isotope in the area corresponding to both adrenals. Although she had no characteristic feature of overt Cushing’s syndrome, her serum cortisol level was not suppressed after an overnight dexamethasone administration. She was diagnosed as having preclinical Cushing’s syndrome. Left adrenalectomy was performed, revealing the well-circumscribed black tumor, mainly consisted of compact cell, in which cytoplasm was filled with numerous granules pigmented with dark to golden brown colors on hematoxylin-eosin staining. These findings suggested that her incidentaloma was a black adrenal adenoma. Production of steroid hormones was confirmed by immunohistochemical analysis of steroidogenic enzymes and by measurement of the tissue contents of hormones, whose levels were comparable with those in adenomas of overt Cushing’s syndrome. This is the first case report of preclinical Cushing’s syndrome resulting from black adrenal adenoma.
    Type of Medium: Online Resource
    ISSN: 1663-2818 , 1663-2826
    URL: Article
    DOI: 10.1159/000079120
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 2540224-9
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  • 5
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    Therapeutic Potential of Thrombomodulin in Renal Fibrosis of Nephrotoxic Serum Nephritis in Wistar-Kyoto Rats
    S. Karger AG ; 2020
    In:  Kidney and Blood Pressure Research Vol. 45, No. 3 ( 2020), p. 391-406
    Details
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 45, No. 3 ( 2020), p. 391-406
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Recombinant human soluble thrombomodulin (rhTM) was approved in 2008 and has been used for treatment of disseminated intravascular coagulation in Japan. The antifibrotic effects of rhTM in acute exacerbation of idiopathic pulmonary fibrosis are well established, but the therapeutic potential of rhTM in renal fibrosis remains poorly understood. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Nephrotoxic serum nephritis (NTS-N) was induced in 22 female Wistar-Kyoto (WKY) rats on day 0. Rats were administered either rhTM or vehicle intraperitoneally, every day from day 4 to day 55. Rats were sacrificed on day 56 when renal fibrosis was established and renal morphological investigations were performed. In vitro, rat renal fibroblasts (NRK-49F) were pretreated with rhTM or saline, and expression levels of profibrogenic gene induced by thrombin were analyzed by real-time reverse transcription polymerase chain reaction. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Compared to WKY-GN-vehicle rats, the body weights of WKY-GN-rhTM rats were significantly greater on day 55. By day 56, rhTM had significantly reduced serum creatinine levels in NTS-N. On the other hand, urinary protein excretion was comparable between the two treatment groups throughout the study. The percentage of Masson trichrome-positive areas in WKY-GN-rhTM rats was significantly lower compared to that in WKY-GN-vehicle rats. Glomerular fibrin deposition was significantly reduced in WKY-GN-rhTM rats. In addition, rhTM significantly reduced the renal cortical mRNA expression levels of TNF-α, Toll-like receptor 4, MYD88, TGF-β, αSMA, collagen I, collagen III, fibronectin, and protease-activated receptor 1 (PAR1), a thrombin receptor. In vitro, thrombin stimulation of NRK-49F cells significantly enhanced the mRNA expression levels of αSMA and PAR1, and these upregulations were significantly reduced by pretreatment with rhTM. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Administration of rhTM after establishment of crescentic glomerulonephritis (GN) attenuated the subsequent development of renal fibrosis in NTS-N, possibly in part by inhibiting thrombin-mediated fibrogenesis. Our results suggest that rhTM may offer a therapeutic option for limiting the progression of chronic kidney disease in crescentic GN.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    URL: Article
    DOI: 10.1159/000506286
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 1482922-8
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  • 6
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    Critical Role of IL-5 in Antigen-Induced Pulmonary Eosinophilia, but Not in Lymphocyte Activation
    S. Karger AG ; 2003
    In:  International Archives of Allergy and Immunology Vol. 130, No. 3 ( 2003), p. 209-215
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 130, No. 3 ( 2003), p. 209-215
    Abstract: Infiltration of antigen-specific CD4+ T cells and production of interleukin (IL)-5 in inflammatory regions play a central role in antigen-induced pulmonary eosinophilia. Genetically IL-5-deficient mice lack antigen-induced airway eosinophilia, but little is known about the role of IL-5 in accumulation and activation of CD4+ T cells in the lung and in airway hyperresponsiveness (AHR). 〈 i 〉 Ascaris suum 〈 /i 〉 extract (Asc) has been used to induce airway eosinophilia and analyze airway inflammation in IL-5 receptor α-chain-deficient (IL-5RKO) mice. We examined the role of IL-5 in CD4+ T cell activation, cytokine production, and AHR upon Asc sensitization. Pulmonary CD4+ T cells in Asc-immunized mice were activated and produced IL-5 upon local exposure to Asc in both wild-type (WT) and IL-5RKO mice. IL-2, IL-4, IL-5, IL-10 and eotaxin were detected in bronchoalveolar lavage fluid of both WT and IL-5RKO mice following exposure to Asc. Airway eosinophilia and AHR were seen only in WT mice, but not in IL-5RKO mice. We conclude that IL-5 appears to be required for the accumulation of eosinophils and AHR in the inflammatory lung. However, IL-5 does not play a critical role in the accumulation of activated CD4+ T cells in the inflammatory lung.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000069513
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2003
    detail.hit.zdb_id: 1482722-0
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  • 7
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    Alteration in Sex-Specific Behaviors in Male Mice Lacking the Aromatase Gene
    S. Karger AG ; 2003
    In:  Neuroendocrinology Vol. 77, No. 6 ( 2003), p. 416-424
    Details
    In: Neuroendocrinology, S. Karger AG, Vol. 77, No. 6 ( 2003), p. 416-424
    Abstract: Brain aromatase (P450arom) is a key enzyme in estrogen biosynthesis from testicular androgens. This local aromatization in neural tissues is thought to be an important process for sexual differentiation and activation of sexual behavior in male rodents. To determine the functional significance of the aromatase gene in development and activation of sex-specific behavior, we analyzed a series of behavioral profiles in gonadally intact male mice with targeted disruption of exons 1 and 2 of the aromatase gene (ArKO). In most cases, ArKO males were infertile and showed deficits in male sexual behavior including mount, intromission and ejaculation. Noncontact penile erection was not significantly affected by deletion of the aromatase gene. A great reduction of aggressive behavior against male intruders was also observed in ArKO males, while they tended to exhibit aggression toward estrous females during male copulatory tests. Furthermore, 73% of ArKO males showed infanticide toward pups, whereas characteristic parental behavior, but not infanticide, was observed in wild-type males. These results support the brain aromatization hypothesis and indicate that aromatase gene expression is a critical step not only for motivational and consummatory aspects of male sexual behavior, but also for aggressive and parental behaviors in male mice.
    Type of Medium: Online Resource
    ISSN: 0028-3835 , 1423-0194
    URL: Article
    DOI: 10.1159/000071313
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2003
    detail.hit.zdb_id: 1483028-0
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  • 8
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    Passive Immunization of the Aβ42(43) C-Terminal-Specific Antibody BC05 in a Mouse Model of Alzheimer’s Disease
    S. Karger AG ; 2005
    In:  Neurodegenerative Diseases Vol. 2, No. 1 ( 2005), p. 36-43
    Details
    In: Neurodegenerative Diseases, S. Karger AG, Vol. 2, No. 1 ( 2005), p. 36-43
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Over the past few years, amyloid beta protein (Aβ) vaccination has become one of the most effective treatments for Alzheimer’s disease.However, the appearance of severe side effects during clinical trials has highlighted the need for improved safety and efficacy.Although antibodies directed against the amino (N)-termini of Aβ are highly effective for passive immunization, a substantial risk of inducing cerebral hemorrhage has been documented. 〈 i 〉 Objective: 〈 /i 〉 We investigated the effect of the administration of BC05, which was the first antibody developed against the carboxyl (C)-termini of Aβ42(43), on the clearance of brain Aβ42(43). 〈 i 〉 Method: 〈 /i 〉 The BC05 antibody was injected into the peritoneal cavity of Tg2576 transgenic mice expressing βAPP 〈 sub 〉 KM670/671NL 〈 /sub 〉 once a week from 3 to 12 months of age. 〈 i 〉 Results: 〈 /i 〉 BC05 caused a selective 44-fold increase in plasma Aβ42(43) and a significant increase in brain soluble Aβ42(43), showing a 156% difference. Brain insoluble Aβ40 and Aβ42(43) levels were decreased by 27.3 and 31.5%, respectively. A reduction in the number of BAN50-labeled plaques was observed. 〈 i 〉 Conclusions: 〈 /i 〉 BC05 might render Aβ42(43) soluble within the brain and inhibit the insoluble deposition of Aβ40 and Aβ42(43). By analyzing the mechanism of the elevation of soluble Aβ42(43) after passive immunization of BC05, safer and more effective methods of immunotherapy for Alzheimer’s disease might be developed.
    Type of Medium: Online Resource
    ISSN: 1660-2854 , 1660-2862
    URL: Article
    DOI: 10.1159/000086429
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2005
    detail.hit.zdb_id: 2126858-7
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  • 9
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    Elevated Levels of Antimicrobial Peptides in Bronchoalveolar Lavage Fluid in Patients with Chronic Eosinophilic Pneumonia
    S. Karger AG ; 2007
    In:  Respiration Vol. 74, No. 1 ( 2007), p. 69-75
    Details
    In: Respiration, S. Karger AG, Vol. 74, No. 1 ( 2007), p. 69-75
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Chronic eosinophilic pneumonia (CEP) is an idiopathic pulmonary disease. As the lung is in direct communication with the environment, inhaled antigen may activate immune mechanisms in the airway that may participate in the pathogenesis of idiopathic pulmonary diseases. Defensins are antimicrobial peptides that consist of α-defensin (HAD) in neutrophils and β-defensin (HBD) in epithelial cells. Defensins act as innate immunity against pathogens acquired from the environment and as mediators to induce local inflammation. 〈 i 〉 Objectives: 〈 /i 〉 The aim of the present study was to determine whether immune mechanisms in the airway are induced in CEP patients. 〈 i 〉 Methods: 〈 /i 〉 We measured BALF defensin levels in patients with CEP, acute EP (AEP) and drug-induced eosinophilic pneumonia (drug-EP). We also measured BALF levels of IL-5, GM-CSF, eotaxin and RANTES. These substances can recruit eosinophils. 〈 i 〉 Results: 〈 /i 〉 BALF HAD levels were higher in patients with CEP than in those with drug-EP and normal controls. HBD-2 was detected in BALF of 10 of 11 CEP patients and in 3 of 5 AEP patients while its level was below detection in drug-EP patients and normal controls. BALF HBD-2 levels correlated with the proportion of lymphocytes in CEP patients. 〈 i 〉 Conclusion: 〈 /i 〉 The defensin-linked immune system is activated in CEP but not in drug-EP. This suggests that inhaled antigen(s) may be involved in the pathogenesis of CEP.
    Type of Medium: Online Resource
    ISSN: 0025-7931 , 1423-0356
    URL: Article
    DOI: 10.1159/000090199
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2007
    detail.hit.zdb_id: 1464419-8
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  • 10
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    Elevated Levels of β-〈i〉D〈/i〉-Glucan in Bronchoalveolar Lavage Fluid in Patients with Farmer’s Lung in Miyazaki, Japan
    S. Karger AG ; 2008
    In:  Respiration Vol. 75, No. 2 ( 2008), p. 182-188
    Details
    In: Respiration, S. Karger AG, Vol. 75, No. 2 ( 2008), p. 182-188
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Farmers may be often exposed to β- 〈 i 〉 D 〈 /i 〉 -glucan in moldy hay, since straw for feed can be stored throughout the year. 〈 i 〉 Objectives: 〈 /i 〉 The aim of the present study was to clarify whether levels of β- 〈 i 〉 D 〈 /i 〉 -glucan, which modifies immune responses, are high in the respiratory tract in farmer’s lung and whether β- 〈 i 〉 D 〈 /i 〉 -glucan participates in the pathogenesis of this condition. 〈 i 〉 Methods: 〈 /i 〉 We measured β- 〈 i 〉 D 〈 /i 〉 -glucan levels in the bronchoalveolar lavage fluid (BALF) of 10 patients with farmer’s lung, 4 with summer-type hypersensitivity pneumonitis (HP) and 10 healthy volunteers. Interleukin (IL)-8 and tumor necrosis factor (TNF)-α levels in BALF were measured by enzyme-linked immunosorbent assay (ELISA). We investigated the effects of β- 〈 i 〉 D 〈 /i 〉 -glucan on nuclear factor (NF)-ĸB activation and on the release of IL-8 and TNF-α from small airway epithelial cells (SAECs) in vitro. 〈 i 〉 Results: 〈 /i 〉 β- 〈 i 〉 D 〈 /i 〉 -Glucan levels in the BALF of farmer’s lung patients were increased compared to those in patients with summer-type HP and in healthy volunteers. Additionally, IL-8 levels in BALF were higher in farmer’s lung than in summer-type HP, and TNF-α levels were equal in the two patient groups but raised compared to those in healthy volunteers. High, but not low, concentrations of β- 〈 i 〉 D 〈 /i 〉 -glucan were found to induce NF-ĸB activation in SAECs. IL-8 levels in the supernatant obtained from SAEC cultures were increased following the addition of β- 〈 i 〉 D 〈 /i 〉 -glucan in vitro. 〈 i 〉 Conclusion: 〈 /i 〉 BALF from farmer’s lung patients showed high β- 〈 i 〉 D 〈 /i 〉 -glucan levels, which may enhance the expression and release of cytokines through NF-ĸB activation in respiratory epithelial cells.
    Type of Medium: Online Resource
    ISSN: 0025-7931 , 1423-0356
    URL: Article
    DOI: 10.1159/000098406
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2008
    detail.hit.zdb_id: 1464419-8
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