Biomedical subjects

Angela Unholzer

Publications and source records attributed to Angela Unholzer.

5 recordsLinked to original sources

PubMed2005

Human defensins.

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12-50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free alpha-helices, extended cysteine-free alpha-helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and beta-sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the alpha-defensins, beta-defensins and the recently described theta-defensins. Mammalian alpha-defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian beta-defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human beta-defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known beta-defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.

Animals↗

PubMed2005

[Gingival Burkitt lymphoma in a hepatitis C-positive renal transplant patient].

Malignant tumors are a frequent complication in the late phase after organ transplantation. Malignant lymphomas are the second most common tumor, exceeded only by cutaneous carcinomas. Compared to the general population, the organ transplant patients have a 30-60 fold increased risk of developing non-Hodgkin's lymphoma. A 55-year-old, hepatitis C-positive man developed an Epstein-Barr virus (EBV)- negative Burkitt lymphoma (BL) first appearing on the gingiva under immunosuppressive therapy nine years after allogenic renal transplantation. He died 37 days after the onset of polychemotherapy. Immediately before his death, meningeal involvement by the BL was diagnosed. BL after organ transplantation is often found at extranodal sites; it involves the central nervous system more frequently than it does in immunocompetent patients. In 70% of BL occurring after organ transplantation, genes or gene products related to EBV can be demonstrated within the tumor cells. The EBV status of the tumor is of important prognostic significance: EBV-positive BL occurring in organ transplant patients usually responds well to reduction or cessation of immunosuppressive therapy; in some cases permanent complete remissions can be achieved even without chemotherapy. In contrast, patients with EBV-negative BL have a very poor prognosis and hardly respond, even to aggressive chemotherapy protocols.

Adult↗

PubMed2003

EGFR, HER-2/neu, cyclin D1, p21 and p53 in correlation to cell proliferation and steroid hormone receptor status in ductal carcinoma in situ of the breast.

Abnormalities in G1/S transition in cell cultures have been attributed to alterations in ErbB (erythroblastic leukaemia viral [v-erb-b] oncogene homologue, avian) signalling, cyclin D1 overexpression or disturbance of the p21(WAF1) (p21)-mediated cell cycle arrest induced by p53. To investigate the significance of these mechanisms on an early stage of human breast tumour growth, we studied the expression of EGFR (ErbB1), HER-2/neu (ErbB2), cyclin D1, p21 and p53 as well as oestrogen (ER) and progesterone receptor (PgR) in paraffin sections of 45 ductal carcinoma in situ (DCIS) by immunohistochemistry. Cell proliferation was assessed by immunohistochemical quantification of Ki-67. Five cases with cyclin D1 overexpression were analysed by FISH for CCND1 amplification. Increased proliferative activity was observed in 46% of DCIS. It was correlated with the expression of EGFR and HER-2/neu (p < 0.05), but neither with cyclin D1 and p21 overexpression nor with p53 accumulation. ErbB positive status was associated with p21 overexpression (p < 0.05). In addition we found a correlation between the overexpression of p21 and cyclin D1 restricted to ErbB-positive cases (p = 0.013). ErbB-negative tumours with increased proliferative activity were ER and cyclin D1 positive. No CCND1 amplification was detected in the analysed cases. In conclusion, our data support that EGFR and HER-2/neu play an important role in cell cycle control in DCIS. p21 appears to be a potential mediator of ErbB signalling. We propose that cyclin D1 could be indirectly induced by ErbB signalling through p21. Besides, ER-mediated upregulation of cyclin D1 seems to be a possible mechanism of maintaining cell proliferation in DCIS in case of EGFR- and HER-2/neu-negativity.

Adult↗

PubMedDate not supplied

High-frequency ultrasound in the evaluation of pharmacological effects on the skin.

In 1987, the introduction of two 20-MHz B- (brightness-) scan ultrasound systems with axial and lateral resolution of 200 microm and 75-80 microm, respectively, rendered two-dimensional sonographic imaging in dermatology possible. Since then cutaneous sonography has increasingly been used to investigate drug effects on human skin. Both unwanted and wanted effects have been studied, including skin thinning due to repeated glucocorticoid application and reduction of skin thickening in hyperplastic disorders such as psoriasis vulgaris due to various treatment approaches. The resolution of 20-MHz ultrasound is sufficient for studying pathological changes and pharmacological effects in the dermis and the subcutaneous fat; for assessing the epidermis, frequencies between 50 and 100 MHz may prove to be more effective.

Administration, Cutaneous↗

PubMedDate not supplied

Different skin thinning potential of equipotent medium-strength glucocorticoids.

In this study, we investigated the effect of prednicarbate, mometasone furoate and betamethasone 17-valerate on total skin thickness over a treatment period of 6 weeks. The study was conducted as a double-blind, placebo-controlled randomized clinical trial with a confirmatory approach. The influence of these drugs on healthy human skin under non-occlusive conditions was assessed by measuring total skin thickness and epidermal thickness using 20 and 50 MHz sonography, respectively. Epidermal surface structure was evaluated using profilometry. Visual assessment addressed signs of atrophy and formation of telangiectasia. The reduction of total skin thickness induced by prednicarbate was clearly less than that caused by betamethasone 17-valerate and mometasone furoate. Prednicarbate led to a higher degree of skin thinning than vehicle. For technical reasons, epidermal thickness could not be reliably evaluated with 50 MHz sonography. Profilometry did not demonstrate any differences between treatments. Visible signs of atrophy or telangiectasia were detected in two subjects each upon betamethasone 17-valerate and mometasone furoate, but not upon prednicarbate or its vehicle. Prednicarbate is a topical glucocorticoid with an improved benefit/risk ratio, as it causes less skin atrophy than the equipotent betamethasone 17-valerate.

Administration, Topical↗