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  • 1
    Digitale Medien
    Digitale Medien
    E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of cutaneous pathology 21 (1994), S. 0 
    Details
    ISSN: 1600-0560
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: To study the temporal and spatial relationship between infiltrating T-cell subsets or eosinophils and cell adhesion molecules on endothelial cells in skin lesions of atopic dermatitis (AD), we undertook immunohistochemical analysis using monoclonal antibodies against surface markers of T cells, eosinophil granule proteins and cell adhesion molecules. Predominant mononuclear cells in acute and chronic skin lesions were CDS, CD4 and CD45RO positive helper-inducer/memory T cells. Their number was significantly and strongly correlated with the intensity of E-selectin expression. Eosinophils and deposition of eosinophil-derived granule proteins such as eosinophil cationic protein (ECP), major basic protein (MBP) and eosinophil peroxidase (EPO) were found constantly in acute lesions and only occasionally in chronic lesions. The total number of immunoreactive eosinophils and deposits of MBP, EPO and ECP were significantly and strongly correlated with die staining intensity of VCAM-1. In chronic lesions significant reduction of VCAM-1 expression paralleled occasional infiltration of eosinophils. Our results demonstrate the possibility that E-selectin and VCAM-1 are the critical adhesion molecules for trafficking of memory T cells and eosinophils, respectively, into skin lesions of AD. Persistent expression of the adhesion molecules may be related to prolongation of the skin lesion in AD.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1600-0560.1994.tb00688.x
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Therapeutic response and potential pitfalls in phase I clinical trials of anticancer agents conducted in Japan (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 451-454 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Key words: Phase I clinical trial – Anticancer agent – Response rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. The published reports of phase I clinical trials of anticancer agents conducted in Japan from 1981 to 1991 were reviewed. A total of 56 clinical studies that evaluated 38 different agents were reviewed. An average of five agents were studied each year. A total of 2200 patients had been recruited into the 56 clinical trials conducted during this period. A total of 91 patients (4.1%) responded to the treatment, with 23 showing a complete response (1.1%) and 48, a partial response (2.2%). In all, 62% of the responses were observed when patients were treated with doses ranging from 76% to 125% of the recommended doses for phase II studies. The response rates obtained for hematological malignancies were higher than those reported for other malignancies. The past status of phase I clinical trials in Japan can be summarized as follows. (1) A median of seven institutes participated in a single trial. The number of institutes participating correlated with the number of patients enrolled. However, too many institutes participated in a single phase I clinical trial in some studies. (2) The median duration of study for the clinical trials was 14 months. The duration of study was too long in some studies, considering the small number of patients enrolled. In conclusion, the methodology of phase I clinical trials of anticancer agents conducted in Japan should be improved in an efficient and scientific manner, especially for the testing of imported agents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685653
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women (1998)
    Springer
    Cancer chemotherapy and pharmacology 42 (1998), S. 1-8 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Key words Pharmacokinetics ; MPA ; Drug-to-drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P〈0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (〈10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002800050777
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  • 4
    Digitale Medien
    Digitale Medien
    Hyporesponsiveness of peripheral blood lymphocytes to streptococcal superantigens in patients with guttate psoriasis: evidence for systemic stimulation of T cells with superantigens released from focally infecting Streptococcus pyogenes (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 382-389 
    Details
    ISSN: 1432-069X
    Schlagwort(e): Key words Psoriasis ; Streptococcus ; Superantigens ; T cell
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Throat infection with Streptococcus pyogenes is the most important trigger for acute guttate psoriasis. We examined the in vitro responses of peripheral blood mononuclear cells (PBMC) to streptococcal superantigens, SPEA and SPEC, and staphylococcal superantigens, SEB and TSST-1, in patients with guttate psoriasis, in patients with chronic plaque psoriasis, and in healthy subjects. PBMC from patients with guttate psoriasis responded poorly to SPEA and SPEC at concentrations of 0.1 and 1 ng/ml as compared with those from patients with plaque psoriasis, but showed high responses to SEB and TSST-1. The hyporesponsiveness recovered after improvement of the skin eruption. There was no significant difference between guttate and chronic types of psoriasis in the percentage of circulating T-cell receptor BV2 or BV8-bearing T cells, responsive to streptococcal superantigens, indicating that T-cell clonal anergy was a mechanism underlying the hyporesponsiveness. Our results suggest that superantigens released from focally infecting S. pyogenes induce a transient activation of relevant T cells, leading to the development of skin eruption and, subsequently, temporary T-cell anergy to these toxins.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004030050426
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Therapeutic response and potential pitfalls in phase I clinical trials of anticancer agents conducted in Japan (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 451-454 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Phase I clinical trial ; Anticancer agent ; Response rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The published reports of phase I clinical trials of anticancer agents conducted in Japan from 1981 to 1991 were reviewed. A total of 56 clinical studies that evaluated 38 different agents were reviewed. An average of five agents were studied each year. A total of 2200 patients had been recruited into the 56 clinical trials conducted during this period. A total of 91 patients (4.1%) responded to the treatment, with 23 showing a complete response (1.1%) and 48, a partial response (2.2%). In all, 62% of the responses were observed when patients were treated with doses ranging from 76% to 125% of the recommended doses for phase II studies. The response rates obtained for hematological malignancies were higher than those reported for other malignancies. The past status of phase I clinical trials in Japan can be summarized as follows. (1) A median of seven institutes participated in a single trial. The number of institutes participating correlated with the number of patients enrolled. However, too many institutes participated in a single phase I clinical trial in some studies. (2) The median duration of study for the clinical trials was 14 months. The duration of study was too long in some studies, considering the small number of patients enrolled. In conclusion, the methodology of phase I clinical trials of anticancer agents conducted in Japan should be improved in an efficient and scientific manner, especially for the testing of imported agents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685653
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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    Artikel (Nationallizenzen)
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