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  • 1
    Electronic Resource
    Electronic Resource
    Effects of long term administration of KUR-1246, a selective β2-adrenoceptor agonist, on pregnant sheep and their fetuses (2005)
    Oxford, UK and Malden, USA : Blackwell Science Ltd
    BJOG 112 (2005), S. 0 
    Details
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective  To evaluate the safety of KUR-1246 as a tocolytic agent, we examined the effects of its long term infusion on respiratory and cardiovascular systems and general metabolism in pregnant sheep and their fetuses.Design  Animal experiment with chronically instrumented ewes and their fetuses.Setting  Center for animal experiments, Hokkaido University School of Medicine, Japan.Sample  Eight Suffolk ewes at 117 to 120 days of gestation.Methods  At 120–124 days of gestation, ewes (n= 4) were infused intravenously for 24 hours with KUR-1246 at 0.03 μg/kg/minute, a dose that completely inhibits oxytocin-induced uterine contractions in pregnant sheep. The controls received saline instead (n= 4). Statistical comparisons were carried out by repeated-measures ANOVA followed by Dunnett's test.Main outcome measures  Maternal and fetal values of heart rate, blood pressure, plasma electrolytes, glucose, insulin and non-esterified fatty acid levels, and blood gases and lactate level.Results  The maternal plasma levels of KUR-1246 increased and reached a plateau at 15 hours or later from the start of the infusion, whereas the fetal levels of it were below the lower limit of quantification (0.1 ng/mL) throughout the experiment. Significant differences over time between the ewes that had received with KUR-1246 and the controls were found for the following parameters: maternal heart rate, blood lactate, plasma glucose, and plasma insulin levels, and fetal plasma glucose and plasma insulin levels (P 〈 0.05). In the KUR-1246 treated ewes, significant changes from the pre-infusion value were detected in maternal blood lactate and fetal plasma glucose levels within 6 hours from the start of the infusion (P 〈 0.05). No significant differences were observed in other parameters in either ewes or fetuses.Conclusion  The physiologic changes induced by a 24-hour infusion of KUR-1246 were transient and considered to be within the compensatory capacity in both pregnant ewes and their fetuses, suggesting that KUR-1246 is a potentially safe tocolytic agent for use by long term infusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-0528.2004.00333.x
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  • 2
    Electronic Resource
    Electronic Resource
    INVOLVEMENT OF TRANSFORMING GROWTH FACTOR-β1 FOR PLATELETS-INDUCED STIMULATION OF ENDOTHELIN-1 PRODUCTION (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 21 (1994), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Possible mechanisms by which platelets stimulate the production of endothelin-1 (ET-1) in vascular endothelial cells (EC) were investigated.2. A supernatant of platelets stimulated the expression of prepro ET-1 mRNA, followed by an increased secretion of ET-1 from cultured EC. These responses were markedly enhanced by pretreatment of the platelets with thrombin, at a concentration which did not influence the ET-1 production in EC. A platelet suspension, separated from cultured EC by a permeable nylon membrane, also markedly stimulated the ET-1 secretion from EC.3. Endothelin-1 production enhanced by the platelet supernatant, with or without thrombin pretreatment, correlated with the active transforming growth factor-β1 (TGF-β1) concentrations in the supernatant. The supernatant-induced increase in ET-1 secretion from the EC was markedly suppressed by TGF-β1 neutralizing antibody.4. We tentatively conclude that platelets stimulate the endothelial ET-1 production by releasing a bioactive diffusible substance, mainly TGF-β1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1994.tb02661.x
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  • 3
    Electronic Resource
    Electronic Resource
    A new method of hernioplasty for adult groin hernias centering on repair of the transversalis fascia (1991)
    Springer
    Surgery today 21 (1991), S. 381-391 
    Details
    ISSN: 1436-2813
    Keywords: adult groin hernia ; transversalis fascia ; Marcy repair ; iliopubic tract repair ; Moschcowitz repair
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method of hernioplasty for adult groin hernias centering on repair of the transversalis fascia was assessed by a questionnaire conducted every five years on adult patients who had received the above operation. The efficacy of this method was evaluated in terms of the postoperative quality of life and prevention of recurrence of groin hernias. Over the last 9 years, 834 adult patients with 921 groin hernias, including bilateral lesions, have undergone the above procedure and overall, favorable results were obtained, with only one case of recurrence (0.1 per cent) being reported. Contralateral herniation, which has been often reported following Bassini's or Hatakoshi's method, was found in only one of our patients although the number of patients who complained of pain in the operated region was comparatively high, being 51 cases or 11.4 per cent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02470965
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  • 4
    Electronic Resource
    Electronic Resource
    Expression of HLA-DR and urokinase-type plasminogen activator in stage IV gastric cancer (1998)
    Springer
    Gastric cancer 1 (1998), S. 71-77 
    Details
    ISSN: 1436-3305
    Keywords: Key words: host immune response, malignant potential, serine protease, fibrinolysis, immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Background. Some patients with stage IV gastric cancer have a long survival. Host immune response and proteolytic activity in the primary tumor may be associated with outcome in these patients. The purpose of this study was to assess prognostic factors in patients with stage IV far advanced gastric cancer. Methods. Findings in 26 patients who underwent resection of stage IV gastric cancer were retrospectively analyzed for clinicopathological variables, and for the immunohistochemical expression of human leukocyte antigen (HLA)-DR as an index of host immune response and for expression of urokinase type-plasminogen activator (u-PA) as an index of proteolytic activity in the tumor. Results. Of the 13 clinicopathological and immunohistochemical variables tested by univariate analysis surgical curability, lymph node metastasis, HLA-DR expression, and u-PA expression had a significant influence on survival after surgery. Multivariate analysis showed that surgical curability, HLA-DR expression, and u-PA expression independently influenced survival. Patients positive for HLA-DR expression [HLA-DR (+)] and regative for u-PA expression [u-PA (−)] had the best survival: 25-month median survival and 25% 5-year survival rate. Patients who were HLA-DR (+) and u-PA (+), or HLA-DR (−) and u-PA (−) had a median survival of 10 months, a 1-year survival rate of 46.2%, and a 2-year survival rate of 7.7%. HLA-DR (−) and u-PA (+) patients had the worst survival: 4.5-month median survival and 0% 1-year survival. Conclusions. These findings suggest that host immune response and proteolytic activity in the primary tumor may determine malignant potential, and that the combination of positive-HLA-DR and negative-u-PA expression in cancer cells may be a predictor of prolonged survival in stage IV gastric cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101200050057
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  • 5
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    Inhibition of interleukin-1β production by extracellular acidification through the TDAG8/cAMP pathway in mouse microglia (2014)
    Wiley-Blackwell
    Details
    Publication Date: 2014-01-23
    Description: Interleukin-1β (IL-1β) is released from activated microglia and involved in the neurodegeneration of acute and chronic brain disorders, such as stroke and Alzheimer's disease, in which extracellular acidification has been shown to occur. Here, we examined the extracellular acidic pH regulation of IL-1β production, especially focusing on TDAG8, a major proton-sensing G-protein-coupled receptor, in mouse microglia. Extracellular acidification inhibited lipopolysaccaride (LPS)-induced IL-1β production, which was associated with the inhibition of IL-1β cytoplasmic precursor and mRNA expression. The IL-1β mRNA and protein responses were significantly, though not completely, attenuated in microglia derived from TDAG8-deficient mice compared with those from wild-type mice. The acidic pH also stimulated cellular cAMP accumulation, which was completely inhibited by TDAG8 deficiency. Forskolin and a cAMP derivative, which specifically stimulates protein kinase A (PKA), mimicked the proton actions, and PKA inhibitors reversed the acidic pH-induced IL-1β mRNA expression. The acidic pH-induced inhibitory IL-1β responses were accompanied by the inhibition of extracellular signal-related kinase (ERK) and c-Jun N -terminal kinase (JNK) activities. The inhibitory enzyme activities in response to acidic pH were reversed by the PKA inhibitor and TDAG8 deficiency. We conclude that extracellular acidic pH inhibits LPS-induced IL-1β production, at least partly, through the TDAG8/cAMP/PKA pathway, by inhibiting ERK and JNK activities, in mouse microglia. This article is protected by copyright. All rights reserved.
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The International Society for Neurochemistry.
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