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Biomedical subjects

F Straube

Publications and source records attributed to F Straube.

6 recordsLinked to original sources

Prevalidation of a new in vitro reconstituted human cornea model to assess the eye irritating potential of chemicals.

This multicentre study aimed at evaluating the reliability (reproducibility) and relevance (predictivity) of a new commercially available human corneal epithelial (HCE) model (SkinEthic Laboratories, Nice, France) to assess acute ocular irritation. A prevalidation approach (protocol optimisation, transfer and performance) was followed and at each of the four participating laboratories, 20 coded reference chemicals, covering the whole range of irritancy, were tested. The compounds were applied topically to the HCE cultures and the level of cytotoxicity (tissue viability and histological analysis) was determined. Once a standardised protocol was established, a high level of reproducibility between the laboratories was observed. In order to assess the capability of the HCE model to discriminate between irritants (I) and non-irritants (NI), a classification prediction model (PM) was defined based on a viability cut-off value of 60%. The obtained in vitro classifications were compared with different in vivo classifications (e.g. Globally Harmonised System) which were calculated from individual rabbit data described in the ECETOC data bank. Although an overall concordance of 80% was obtained (sensitivity = 100% and specificity = 56%), the predictivity of the HCE model substantially increased when other sources of in vivo and in vitro data were taken into account.

Cornea↗

[Multi-modality therapy concept in metastatic follicular thyroid carcinoma with hyperthyroidism].

The coincidence of hyperthyroidism and thyroid carcinoma seldom occurs. Only few reports on functionally metastases of thyroid carcinoma have been published. We report a 59-year-old man who underwent subtotal thyroidectomy for toxic nodular goiter. Histological examination revealed a follicular thyroid carcinoma. After thyroidectomy and cervical lymphadenectomy the patient developed a strong hyperthyreosis. Scintigraphy showed strong radioiodine uptake in the sacrum. De-bulking resection of the metastasis followed by high-dose radioiodine treatment was performed. After radioiodine therapy the patient became euthyroid. Treatment of hyperthyreosis in metastatic thyroid cancer requires a multimodal therapeutic concept.

Adenocarcinoma, Follicular↗

Differential modulation of CD8beta by rat gammadelta and alphabeta T cells after activation.

Major histocompatibility complex (MHC) class I-restricted alphabeta T cells express the CD8alphabeta heterodimer, which acts as a MHC class I-specific co-receptor. Rats are so far the only species with frequent expression of the CD8alphabeta by MHC-unrestricted gammadelta T cells. This study compares CD8alphabeta expression by splenic rat alphabeta and gammadelta T cells and reveals a lineage-specific difference in the control of CD8beta expression. After activation in vitro, many gammadelta T cells, but not alphabeta T cells, persistently down-modulate the expression of CD8beta, but not CD8alpha, at the RNA level. Down-regulation occurred after stimulation with T-cell receptor (TCR)-specific monoclonal antibody (mAb) and interleukin-2 (IL-2) or CD28-mediated costimulation, and after activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Functional differences between modulating and non-modulating cells were not found with respect to interferon-gamma (IFN-gamma) production and cytolytic activity. The modulation could be indicative for a fundamental difference between alphabeta and gammadelta T cells and also limits the use of CD8beta as a stable marker of gammadelta T-cell subsets. Possibly, CD8beta modulation provides a mechanism to escape over-stimulation by (auto-)antigens by increasing the threshold of TCR-mediated activation in gammadelta T cells.

Animals↗

Expression of functional CD8alpha Beta heterodimer on rat gamma delta T cells does not correlate with the CDR3 length of the TCR delta chain predicted for MHC class I-restricted antigen recognition.

In accordance with their lack of MHC restriction, most mouse and human gamma delta T cells express neither the CD4 nor CD8(alpha beta) coreceptor. In striking contrast, up to 80% of splenic rat gamma delta T cells express the CD8alpha beta isoform of CD8, which for the alpha beta T cell subset serves as a marker for MHC class I-restricted cells. We compared CD8 on alpha beta and gamma delta T cells with regard to co-stimulatory function and correlation of CD8 expression with TCRDV usage and CDR3delta length. In both subsets, CD8 acted as a co-stimulatory molecule in vitro and was found to bind the kinase lck efficiently. No differences between the CDR3delta length spectra of CD8+ and CD8- gamma delta T cells or between unselected thymic and peripheral gamma delta T cells were found. As seen in man and mice, CDR3delta were rather long, a structural feature which can be expected to interfere with an alpha beta TCR-like mode of MHC class I binding. In summary, CD8 expressed by rat gamma delta T cells is a molecule with the potential to act as a coreceptor, but its expression gives no indication for antigen recognition analogous to that of MHC class I-restricted alpha beta T cells.

Animals↗

[Quantitative vascular analysis in the marginal periodontium using PECAM-1].

BACKGROUND: Systemic sclerosis (SSc) is a generalized disorder of the interstitial tissues and vasculature with distinct abnormalities in three systems, immune and autoimmune, vascular and microvascular, and mesenchymal extracellular matrix (ECM), that lead to exuberant fibrosis. The aim of this study was to compare the number of blood vessel profiles in the marginal gingiva between SSc patients and patients with periodontitis but without SSc by using biopsies. METHODS: Marginal gingiva and gingival papilla were obtained from 13 scleroderma patients and 8 patients with periodontitis after routine tooth extraction and gingival curettage. On the histological sections, immunohistochemical investigations were performed using the avidin-biotin complex method (ABC) and the monoclonal antibody CD 31/Clone JC70A (platelet endothelial cell adhesion molecule-1). Blood vessels were identified by light microscopy (original magnification x400) and counted within 0.3615 mm2. Medians of blood vessel profiles were compared by Mann-Whitney U-test. RESULTS: There is no statistical difference between the median of blood vessel profiles in the marginal gingiva of SSc patients as compared to the median of blood vessel profiles in the marginal gingiva of patients with periodontitis (P = 0.665). We did not discover avascular areas in the subepithelial connective tissue. DISCUSSION: The pathological changes in the microvasculature in the dermis of SSc patients are not transferable to the marginal periodont, as intraindividual histological examinations of dermis and oral mucosa in relation to the degree of the disease are not available yet.

Adult↗

Female sex hormones decrease constitutive endothelin-1 release via endothelial sigma-1/cocaine receptors: an action independent of the steroid hormone receptors.

Cardiovascular disease is rare in premenopausal women compared to men. The authors investigate sex hormone-induced endothelin-1 (ET-1) release and the involvement of classic sex hormone receptors as well as the ability of sigma-1/cocaine receptors to respond to sex hormones. ET-1 release was measured in the supernatant of endothelial cells after treatment with beta-estradiol, progesterone, testosterone, or combined with their antagonists, and with the sigma-1 receptor ligand ditolylguanidine (DTG), or haloperidol, a sigma-1 receptor antagonist. Binding assays were performed using 2.5 x 10(-8) M [3H]DTG. Female sex hormones decreased ET-1 release whereas testosterone increased it, sex hormone antagonists only slightly attenuated or had no effect on the respective hormone's effect. DTG totally blocked the female sex hormone-induced inhibition on ET-1 release, whereas testosterone-induced stimulation was not affected. However, haloperidol blocked both. [3H]DTG binding was displaced by beta -estradiol but not by testosterone. DTG-binding sites account for 513 +/- 114 per cell, KD 8.79 nM. These data suggest that besides classic steroid hormone receptors, sigma-1/cocaine receptors mediate the effects of female sex hormones on ET-1 release, an up to now unknown signalling pathway. Results also suggest that female and male sex hormones may bind to different sites on sigma-1 receptors, exerting opposite pharmacological effects.

Animals↗