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  • 1
    In: Oncology, S. Karger AG, Vol. 57, No. 4 ( 1999), p. 318-323
    Abstract: To determine the predictive value of the expression of p53 and glutathione S-transferase-π (GST-π) with respect to chemotherapy response, immunostaining was performed on transbronchial biopsy specimens from previously untreated patients with non-small cell lung cancer. Of the 54 patients, 34 patients (63%) and 37 patients (69%) were positive for p53 and GST-π, respectively. The response rates in the p53-positive and p53-negative group were 15 and 45%, and those in GST-π-positive and GST-π-negative groups were 16 and 47%, respectively. A multiple logistic regression analysis revealed that positive immunostaining for GST-π was a significant risk factor for clinical chemotherapy resistance. The combination of these two markers was the most important independent factor in predicting a response to chemotherapy in multiple logistic regression analysis. Immunohistochemical expression of p53 and GST-π was independently related to clinical chemoresistance in patients with non-small cell lung cancer. Combined use of these two biomarkers may be a useful predictor of clinical chemoresistance.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1999
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 2
    In: Chemotherapy, S. Karger AG, Vol. 48, No. 4 ( 2002), p. 205-210
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Previous studies have reported a synergistic effect between irinotecan and cisplatin. We have conducted a phase I trial combining these agents to find the optimal dose of irinotecan in combination with a fixed dose of cisplatin. 〈 i 〉 Methods: 〈 /i 〉 Patients with advanced solid tumors, aged ≤75 years, performance status ≤2, and adequate organ function were enrolled in this study. They were treated at 4-week intervals with irinotecan plus 20 mg/m 〈 sup 〉 2 〈 /sup 〉 cisplatin on days 1, 8, and 15. The starting dose of irinotecan of 40 mg/m 〈 sup 〉 2 〈 /sup 〉 was escalated in 10 mg/m 〈 sup 〉 2 〈 /sup 〉 increments until a maximum dose of 90 mg/m 〈 sup 〉 2 〈 /sup 〉 was reached. 〈 i 〉 Results: 〈 /i 〉 The recommended dose for phase II studies is 90 mg/m 〈 sup 〉 2 〈 /sup 〉 of irinotecan and 20 mg/m 〈 sup 〉 2 〈 /sup 〉 of cisplatin on days 1, 8, and 15. Overall response to the chemotherapy was 35% (95% confidential interval, 19.2–54.6%). 〈 i 〉 Conclusion: 〈 /i 〉 This combination seems to be active against lung cancer with acceptable toxicity. A phase II study is now ongoing.
    Type of Medium: Online Resource
    ISSN: 0009-3157 , 1421-9794
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 1482111-4
    SSG: 15,3
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  • 3
    In: Pathobiology, S. Karger AG, Vol. 73, No. 1 ( 2006), p. 1-7
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 Saliva secretion is mediated by cAMP and the calcium signaling pathway in salivary acinar cells. The PKA signaling pathway plays an important role in protein secretion through the activation of cAMP, in fluid secretion through the elevation of intracellular calcium and in the activation of cAMP response element-binding protein (CREB), which is involved in these signaling cascades. In this study, we investigated whether the activation of CREB plays a part in the salivary secretion in mice. 〈 i 〉 Methods: 〈 /i 〉 We examined CREB activation by assessing phosphorylation at the serine-133 position using Western blotting. 〈 i 〉 Results: 〈 /i 〉 Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a β-adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol and isoproterenol-induced CREB phosphorylation was blocked by atropine (a muscarinic acetylcholine antagonist) and propranolol (a β-adrenergic antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol-stimulated amylase secretion from parotid acinar cells was inhibited by H89 and adenoviral dominant-negative CREB. 〈 i 〉 Conclusion: 〈 /i 〉 These results indicate that the muscarinic and β-adrenergic activation of CREB was mediated through the PKA pathway and that CREB is involved in protein secretion from parotid acinar cells.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1483541-1
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    S. Karger AG ; 2012
    In:  ORL Vol. 74, No. 4 ( 2012), p. 208-210
    In: ORL, S. Karger AG, Vol. 74, No. 4 ( 2012), p. 208-210
    Abstract: 〈 b 〉 〈 i 〉 Purpose: 〈 /i 〉 〈 /b 〉 The aim of this study was to establish a method to observe vocal fold vibration using a low-cost high-speed laryngeal imaging system. 〈 b 〉 〈 i 〉 Procedures: 〈 /i 〉 〈 /b 〉 We assembled a high-speed imaging system with a consumer digital camera and a rigid laryngeal endoscope. The camera can shoot digital images at a rate of 1,200 frames per second and be purchased for about USD 1,000 in Japan. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We examined the normal and pathological vocal folds of 215 subjects with our new system and analyzed the vocal fold vibration in these subjects by playback of a video and kymograph images. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our high-speed laryngeal imaging system is highly cost-effective and can be a useful tool for examining the vocal folds of patients with voice disorders.
    Type of Medium: Online Resource
    ISSN: 0301-1569 , 1423-0275
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483533-2
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  • 5
    In: Neuropsychobiology, S. Karger AG, Vol. 46, No. 3 ( 2002), p. 136-140
    Abstract: Genetic polymorphism of the serotonin 5-HT 〈 sub 〉 2A 〈 /sub 〉 receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel –1438G/A polymorphism in the promoter region of the 5-HT 〈 sub 〉 2A 〈 /sub 〉 receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Åsberg Depression Rating Scale scores showed no significant difference among –1438G/G, –1438G/A, and –1438A/A genotype groups. The results demonstrated that the –1438G/A promoter polymorphism in the 5-HT 〈 sub 〉 2A 〈 /sub 〉 receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.
    Type of Medium: Online Resource
    ISSN: 0302-282X , 1423-0224
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 1483094-2
    SSG: 5,2
    SSG: 15,3
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  • 6
    In: Neuropsychobiology, S. Karger AG, Vol. 66, No. 3 ( 2012), p. 185-192
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Two opposing models for the action of ghrelin in the behavioral responses to stress were recently proposed. Some studies suggest that an increase in ghrelin contributes to the mechanisms responsible for the development of stress-induced depression and anxiety, while others suggest that it helps minimize what otherwise would be more severe manifestations of depression and anxiety following stress. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We measured serum ghrelin levels, Profile of Mood States (POMS) scores and State-Trait Anxiety Inventory scores in nonresponders (treatment-resistant patients; 30) and responders (38) with major depressive disorder (MDD), nonresponders (29) and responders (51) with panic disorder and 97 healthy controls. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The ghrelin concentration in nonresponders with MDD was higher than that of responders with MDD and normal controls. The ghrelin concentration in nonresponders with panic disorder was higher than that of normal controls. POMS vigor scores in patients with MDD and panic disorder were significantly decreased compared with those in healthy controls. Other POMS scores in patients with MDD and panic disorder were significantly increased compared with those of healthy controls. Trait and state anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients were higher than those in healthy controls. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 These results indicate that decreased serum ghrelin levels might be associated with antidepressant treatment to confer the maximum therapeutic effect in patients with MDD and panic disorder.
    Type of Medium: Online Resource
    ISSN: 0302-282X , 1423-0224
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483094-2
    SSG: 5,2
    SSG: 15,3
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  • 7
    In: Cardiology, S. Karger AG, Vol. 105, No. 1 ( 2006), p. 61-66
    Abstract: 〈 i 〉 Backgrounds: 〈 /i 〉 Although long-term treatment with beta-blockers has been shown to improve morbidity and mortality in dilated cardiomyopathy (DCM), patient re- sponses are heterogeneous. 〈 i 〉 Methods: 〈 /i 〉 To establish the appropriate indication for the initiation of beta-blocker therapy, we retrospectively analyzed 38 DCM patients treated with beta-blockers (metoprolol or carvedilol) and examined differences in baseline profiles between patients who could continue the therapy (responders) and those who could not (non-responders). 〈 i 〉 Results: 〈 /i 〉 In 13 non-responders, the duration from onset of symptoms to beta-blocker initiation was longer (p 〈 0.05), systolic blood pressure was lower (p 〈 0.001), serum sodium concentration was lower (p 〈 0.05), left ventricular posterior wall thickness was thinner (p 〈 0.05), left ventricular end-diastolic pressure was higher (p 〈 0.05) and left ventricular wall stress was lower (p 〈 0.05) than in 25 responders. In 19 patients receiving carvedilol, 5 non-responders showed higher levels of human atrial natriuretic peptide (p 〈 0.05) and brain natriuretic peptide (p 〈 0.01) than 13 responders. Discriminant analysis with a linear discriminant function showed the following equation predicted response to beta-blocker therapy: h = 0.004 × systolic blood pressure – 0.002 × brain natriuretic peptide + 0.667 (R 〈 sup 〉 2 〈 /sup 〉 = 0.67, p 〈 0.001). The probability of predicting the response was 94.1% with h ≧0.5. 〈 i 〉 Conclusion: 〈 /i 〉 We conclude that h≧0.5 is the appropriate indication for the initiation of beta-blocker therapy in DCM.
    Type of Medium: Online Resource
    ISSN: 0008-6312 , 1421-9751
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1482041-9
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  • 8
    In: Acta Cytologica, S. Karger AG, Vol. 43, No. 3 ( 1999), p. 457-463
    Type of Medium: Online Resource
    ISSN: 1938-2650 , 0001-5547
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1999
    detail.hit.zdb_id: 2256676-4
    SSG: 12
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  • 9
    In: Cerebrovascular Diseases Extra, S. Karger AG, Vol. 9, No. 1 ( 2019-4-30), p. 25-30
    Abstract: 〈 b 〉 〈 i 〉 Background/Purpose: 〈 /i 〉 〈 /b 〉 Because atherosclerotic factors and antithrombotic agents sometimes induce cerebral microbleeds (CMBs), patients with cerebral large artery disease (CLAD) tend to have more CMBs than control subjects. On the other hand, VEGF contributes to the disruption of the blood-brain barrier, and it may induce parenchymal edema and bleeding. We conducted a study to evaluate the role of vascular endothelial growth factor (VEGF) in the occurrence of CMBs in patients with CLAD. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 CLAD is defined as stenosis or occlusion of either the carotid artery or the middle cerebral artery of 50% or more. We prospectively registered patients with CLAD who were hospitalized in our neurocenter. Biological backgrounds, atherosclerotic risk factors, administration of antithrombotics before hospitalization, and levels of cytokines and chemokines were evaluated. Susceptibility-weighted imaging or T2*-weighted MR angiography was used to evaluate CMBs. The Brain Observer MicroBleed Scale (BOMBS) was used for CMB assessments. Images were analyzed with regard to the presence or absence of CMBs. We also examined plasma VEGF concentrations using a commercial ELISA kit. Because more than half showed plasma VEGF levels below assay detection limits (3.2 pg/mL), the patients were dichotomized by plasma VEGF levels into two groups (above and below the detection limit). After univariate analyses, logistic regression analysis was conducted to determine the factors associated with the CMBs after adjustment for age, sex, the presence of hypertension, and administration of antithrombotic agents. A similar analysis with CMBs separated by location (cortex, subcortex, or posterior circulation) was also conducted. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Sixty-six patients (71.1 ± 8.9 years, 53 males and 13 females) were included in this study. Plasma VEGF levels were not correlated with age, sex, and atherosclerotic risk factors; however, patients with VEGF levels & #x3e;3.2 pg/mL tended toward more frequent CMBs (60.0 vs. 32.6%, in the presence and absence of CMBs, 〈 i 〉 p 〈 /i 〉 = 0.056). With regard to the location of CMBs, those in the cortex and/or at the gray-white junction were observed more frequently in the patients with VEGF levels & #x3e;3.2 pg/mL after multivariable analyses (odds ratio: 3.80; 95% confidence interval: 1.07–13.5; 〈 i 〉 p 〈 /i 〉 = 0.039). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In patients with CLAD, elevated plasma VEGF might be associated with CMBs, especially those located in the cortex and/or at the gray-white junction.
    Type of Medium: Online Resource
    ISSN: 1664-5456
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 2651613-5
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  • 10
    Online Resource
    Online Resource
    S. Karger AG ; 2006
    In:  European Neurology Vol. 55, No. 3 ( 2006), p. 145-150
    In: European Neurology, S. Karger AG, Vol. 55, No. 3 ( 2006), p. 145-150
    Abstract: We investigated changes in neuropsychological function in patients with carotid stenosis following carotid endarterectomy (CEA) in relation to cerebral hemodynamics. The subjects were 24 patients who underwent CEA and 17 healthy controls matched by age, educational level, gender and handedness. Cerebral angiography, single-photon emission computed tomography (SPECT) and neuropsychological tests were performed approximately 1 week before and 3 weeks after CEA in all patients. In the patient group, the categories achieved in the new modified Wisconsin Card Sorting Test (WCST) improved significantly after CEA (4.0 ± 2.0; before CEA: 2.3 ± 2.1, p 〈 0.01). The perseverative errors of Nelson in the WCST improved significantly (before CEA: 9.1 ± 6.9, after CEA: 3.3 ± 3.4, p 〈 0.01). The difficulty maintaining set in the WCST improved significantly (before CEA: 2.3 ± 1.9, after CEA: 1.3 ± 1.7, p 〈 0.05). In the control group, none of the test scores showed significant improvement between the first and second tests. Moreover, frontal lobe function improved significantly in those patients with baseline carotid artery diameter of more than 70% of normal, or whose preoperative cerebral perfusion reserve was reduced by less than 15% of a response to acetazolamide. Our results suggest that CEA improves frontal lobe function in patients with severe carotid stenosis or reduced cerebral perfusion reserve.
    Type of Medium: Online Resource
    ISSN: 0014-3022 , 1421-9913
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1482237-4
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