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  • 1
    Abstract: Inducible serum proteins whose concentrations oscillate between nontolerogenic and tolerogenic levels pose a particular challenge to the maintenance of self-tolerance. Temporal restrictions of intrathymic antigen supply should prevent continuous central tolerization of T cells, in analogy to the spatial limitation imposed by tissue-restricted antigen expression. Major acute-phase proteins such as human C-reactive protein (hCRP) are typical examples for such inducible self-antigens. The circulating concentration of hCRP, which is secreted by hepatocytes, is induced up to 1,000-fold during an acute-phase reaction. We have analyzed tolerance to hCRP expressed in transgenic mice under its autologous regulatory regions. Physiological regulation of basal levels (〈10(-9) M) and inducibility (〉500-fold) are preserved in female transgenics, whereas male transgenics constitutively display induced levels. Surprisingly, crossing of hCRP transgenic mice to two lines of T cell receptor transgenic mice (specific for either a dominant or a subdominant epitope) showed that tolerance is mediated by intrathymic deletion of immature thymocytes, irrespective of widely differing serum levels. In the absence of induction, hCRP expressed by thymic medullary epithelial cells rather than liver-derived hCRP is necessary and sufficient to induce tolerance. Importantly, medullary epithelial cells also express two homologous mouse acute-phase proteins. These results support a physiological role of "ectopic" thymic expression in tolerance induction to acute-phase proteins and possibly other inducible self-antigens and have implications for delineating the relative contributions of central versus peripheral tolerance.
    Type of Publication: Journal article published
    PubMed ID: 9653079
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  • 2
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Key words C 1-inhibitor deficiency ; Angioedema ; Non-Hodgkin's lymphoma ; Complement factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two cases of lymphoma-associated acquired C 1-inhibitor deficiency are described. In both patients, C 1-inhibitor deficiency and related symptoms preceded the diagnosis of the underlying neoplasm by several months. C 1-inhibitor deficiency was most likely due to consumption following immunocomplex formation. In both patients, a close relationship between low levels of C 1-inhibitor and tumor relapse was observed during follow-up. These findings indicate that measurement of C 1-inhibitor and complement factor C4 can be used as markers of disease activity in affected patients.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report the efficacy and toxicity of combined methotrexate, vinblastine, 4′-epirubicin and cisplatin (M-VEC) for the treatment of advanced urothelial tract tumors in 58 evaluable patients. Histologically, the patients had pure transitional-cell carcinoma (89.7%), squamous-cell carcinoma (8.6%) and anaplastic carcinoma (1.7%). Locally advanced disease (pT3-4 N0 M0) was present in 22 patients (37.9%); pelvic lymphnode metastases (pT3-4 N1-3 M0), in 20 (34.5%); and metastatic disease, in 16 (27.6%). Response was observed in 72.3% of the patients, with complete remission achieved by 51.7%. Response rates and survival were influenced by histological subtype and tumor stage. Squamous-cell carcinoma did not respond to M-VEC chemotherapy. There was one drug-related death (1.7%); otherwise, toxicity was mild to moderate. Adverse effects included cardiac toxicity (9%), mucositis (5.1%), nadir sepsis (1.7%) and renal failure (1.7%) in a small number of patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1569-8041
    Keywords: brain metastases ; germ-cell cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To examine the feasibility and efficacy of first-linehigh-dose chemotherapy (HD-CTX) in patients with advanced metastatic germ-celltumors (GCT) and brain metastases. Patients and methods:Twenty-two patients with brain metastasesat initial diagnosis were identified within a cohort of two hundred thirty-oneconsecutive patients with advanced metastatic disease, entered on a Germanmulticenter trial between January 1993 and July 1998. All patients receivedfirst-line HD-CTX with cisplatin–etoposide–ifosfamide (HD-VIP)followed by autologous stem-cell transplantation. Brain irradiation (BRT) with30–50 Gy ± 10 Gy boost was applied in patients with symptomaticCNS disease or as consolidation in case of residual CNS lesions after HD-CTX. Results:A median number of 4 HD-CTX cycles (range 2–5) wereapplied to the 22 patients. Ten patients received HD-CTX alone and twelvepatients were treated with HD-CTX plus BRT. Median duration of WHO grade 4granulocytopenia and thrombocytopenia was seven and five days after eachcycle, respectively. Non-hematologic toxicity consisted mainly ofmucositis/enteritis (WHO grade 3–4 32%). Two early deathsoccurred in twenty-two patients (one CNS-bleeding/one sepsis). Fourteen oftwenty patients achieved a CR/PRm− status. Twenty patients (91%)responded in the brain (55% CR/36% PR). Two-yearprogression-free and overall survival rates were 72% and 81%,respectively. These survival rates are substantially higher compared to theavailable data in the literature. Conclusions:High-dose chemotherapy with autologous stem-cellsupport ± BRT appears to be feasible without increased therapy-relatedmortality in patients with advanced metastatic GCT and brain metastases. Theresults achieved emphasize the high chemosensitivity of CNS metastases fromGCT and suggest a potential role for dose intensification. The dose of BRT inaddition to HD-CTX may be tailored to the presence of clinical symptoms andthe response of CNS metastases to chemotherapy.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-2622
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On rapporte une série expérimentale (12 lapins) par laquelle on montre les relations fonctionelles entre la tension intra-oculaire, la pression sanguine et le volume minute de la carotide homolatérale. Des mensurations au repos et des mensurations après pincement manuel de l'aorte abdominale ont été faites. D'abord les valeurs de mensuration d'un seul animal étaient examinées par une analyse de régression simple et multiple. La pression sanguine de la carotide et la tension intra-oculaire étaient liées par une certitude de mesure B de 71 %. La courbe de la regression a été reproduite. B était considérablement plus petit pour la relation entre le volume minute de la carotide et la tension intra-oculaire (20%). Les deux facteurs, la pression sanguine et le volume minute, ont déterminé la tension intra-oculaire par 89%. Cette valeur est certainement trop élevée pour le collectif. Cependant nous espérons avoir montré clairement que les facteurs essentiels de la circulation, la pression sanguine et le volume du courant du sang (/zzStromvolume”), ont une influence déterminante sur la pression intra-oculaire normale.
    Abstract: Summary This report is on an experimental series which was carried out on twelve rabbits. It was made to show the functional relation between intra-ocular pressure, blood pressure and minute volume of the homolateral carotis communis. Static measurements and measurements after manually clamping-off the abdominal aorta were evaluated. Primarily the measurement values of only one animal were analysed by means of a simple and multiple regression analysis. Blood pressure of the carotis communis and intra-ocular pressure were connected with each other by a precision measurement (B) of 71%. Their regression-curve was shown. Considerably smaller was B for the relation between minute volume of the carotis communis and intra-ocular pressure (20%). Both factors, blood pressure and minute volume, determined to 89% the intra-ocular pressure. This value surely is super-elevated for the collective. Yet we believe to have made clear that the basal circulatory factors, blood pressure and flow volume have decisive influence on the level of the normal intra-ocular pressure.
    Notes: Zusammenfassung Es wird über eine an 12 Kaninchen durchgeführte Versuchsreihe berichtet, die die funktionellen Beziehungen zwischen Augeninnendruck, Blutdruck und Minutenvolumen der homolateralen Carotis communis aufzeigen sollen. Ausgewertet wurden Ruhemessungen und Messungen nach manueller Abklemmung der Bauchaorta. Zuerst wurden die Meßwerte nur eines Tieres mittels einfacher und multipler Regressionsanalyse untersucht. Blutdruck der Carotis communis und Augeninnendruck waren mit einem Bestimmtheitsmaß B von 71% miteinander verknüpft. Die Regressionskurve wurde abgebildet. Wesentlich geringer war B für die Relation zwischen Minutenvolumen der Carotis communis und intraokularem Druck (20%). Beide Faktoren, Blutdruck und Minutenvolumen, bestimmten zu 89% den intraokularen Druck. Dieser Wert ist für das Kollektiv sicherlich überhöht. Dennoch glauben wir, deutlich gemacht zu haben, daβ die basalen Kreislauffaktoren, Blutdruck und Stromvolumen, von maβgebendem Einfluβ auf die Höhe des normalen intraokularen Druckes sind.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0878
    Keywords: Key wordsGli ; Polydactyly ; Mutations ; Shh ; Limb development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract During development of the limb Shh plays a key role as a mediator of zone of polarizing activity (ZPA). However, the molecular mechanisms by which Shh directs anterior/posterior patterning in the limb remain unknown. Members of the Gli gene family encode zinc-finger transcription factors and represent likely candidates for being regulators of Shh target genes. In this review we would like to summarize the current knowledge on expression and function of Gli genes in limb development.
    Type of Medium: Electronic Resource
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