Concerning allergic diseases, the incidence of allergic symptoms, as well as their severity, seems to decrease with age. The decline of onset of allergic symptoms observed in ageing might result from ...a decrease of serum total and specific IgE. Atopic disorders are complex diseases that involve interactions among several physiological systems, e.g. skin, lung, mucosae, and the immune system. It was the aim of this study to compare the effects of age on total and specific IgE in patients with atopic dermatitis (AD), allergic rhinitis or asthma, and insect allergy, respectively.The study population consisted of 559 individuals (male: 229 and female: 330). Total and allergen specific IgE was measured in every individual. From the whole study population, 113 patients suffered from atopic dermatitis (AD), 132 had allergic rhinitis or asthma, and 314 were tested because of insect allergy. Total and specific serum IgE was significantly decreased as a function of age in patients with allergic rhinitis and asthma and with insect allergy. In contrast, no significant decrease of total and specific serum IgE in old individuals with AD was observed. Additionally, in the group of patients with a total IgE < 300 kU/l a reduction of total serum IgE was significantly correlated with age. In contrast, patients with IgE levels > 300 kU/l showed no correlation with age.Immunosenescence does not affect increased IgE levels in atopic patients with AD and/or high serum IgE levels indicating that in these subgroups of patients the atopic propensity remains into advanced age. One may hypothesize that either onset of allergic sensitization during life or the kind of atopic disease influences the correlation between age and IgE synthesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct
association between in vitro and in vivo ...chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy
of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between
in vitro sensitivity and therapy outcome.
Patients and Methods: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free
survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five
drug combinations using an ATP-based luminescence viability assay.
Results: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all
study end points (per protocol). The drug combinations used were gemcitabine + treosulfan, paclitaxel + cisplatin, paclitaxel
+ doxorubicin, and gemcitabine + cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and
31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients
compared with 16.1% in chemoresistant patients ( P = 0.114); progression arrest (complete response + partial response + stable disease) was 59.1% versus 22.6% ( P = 0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant
patients ( P = 0.041).
Conclusion: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome
of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated
by a planned phase III trial using a randomized, standard-regimen controlled setting.
Computational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of ...tissues. Here we show an approach which is able to computationally turn a healthy in silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (τ). Prolonging τ results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells and (4) a marked reduction in turnover time. The prolongation of τ is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency.
Contact: niels.grabe@med.uni-heidelberg.de
Melanocytic schwannoma is a rare soft-tissue tumor, which arises most commonly in the paraspinal sympathetic chain. In general, 25% of the patients develop metastasis. To date, only 17 cases of a ...cutaneous and subcutaneous melanocytic schwannoma have been reported. None of these patients developed metastasis. Three cases of cutaneous melanocytic schwannoma, diagnosed in our institution are reported. For further literature overview we performed a search on Medline using the terms 'melanocytic schwannoma' or 'melanotic schwannoma' or 'Carney complex' combined with 'skin' or 'cutaneous', for the period 1970-2007. Seventeen patients were described to have melanocytic schwannoma of the skin or subcutaneous tissues. These papers were reviewed for clinical data. Two of the three patients showed metastatic disease, one of them died of disseminated metastases. In contrast, none of the reported cases of cutaneous or subcutaneous melanocytic schwannomas was characterized by a malignant course. The differential diagnosis, especially with regard to malignant melanoma, is made by histology and by its clinical course, which differs from melanoma in its tendency to recur at the site of excision and slow rate of growth. Commonly misdiagnosed as melanoma, this tumor reveals insights into the origin of both melanocytes and Schwann cells. It is likely that the biological bases for melanoma and melanocytic schwannoma differ. It is necessary to differentiate this tumor from melanoma because of the differing prognosis and the association of melanocytic schwannoma with the Carney complex. Owing to the lack of clinical trials, we recommend that patients be treated according to the existing guidelines for melanoma.
Motivation: Systems biology is currently focused on integrating intracellular networks, although clinically, diseases are largely defined by their histological features. For example, no computational ...model can simulate today the formation of a horizontally layered epidermis. Since the epidermis is the most complex structured epithelial tissue, systems biology models could yield important insights in epithelial tissue, in which most of all human cancers arise. Results: We describe the algorithms of a system, capable of simulating the tissue homeostasis in human epidermis leading to a horizontally layered tissue with cells of different differentiation stages. The system predicts epidermal morphology, tissue kinetics and 2D flow of Ca2+ ions. Predicted properties of an epidermis with a healthy and a disturbed barrier are compared with the literature. The system closely mimics the respecting physiological situations. Availability: Additional information and films of the simulation are available at the website. Source code is available on request. http://www.zbh.uni-hamburg.de/research/ESB/index.php Contact: grabe@zbh.uni-hamburg.de
MOTIVATION: Systems biology is currently focused on integrating intracellular networks, although clinically, diseases are largely defined by their histological features. For example, no computational ...model can simulate today the formation of a horizontally layered epidermis. Since the epidermis is the most complex structured epithelial tissue, systems biology models could yield important insights in epithelial tissue, in which most of all human cancers arise. RESULTS: We describe the algorithms of a system, capable of simulating the tissue homeostasis in human epidermis leading to a horizontally layered tissue with cells of different differentiation stages. The system predicts epidermal morphology, tissue kinetics and 2D flow of Ca super(2+) ions. Predicted properties of an epidermis with a healthy and a disturbed barrier are compared with the literature. The system closely mimics the respecting physiological situations. AVAILABILITY: Additional information and films of the simulation are available at the website. Source code is available on request. http://www.zbh.uni-hamburg.de/research/ESB/index.php CONTACT: grabebh.uni-hamburg.de
There is increasing evidence that the Fas/Fas ligand (FasL) system is involved in tumor-mediated immune suppression. The purpose of this study was to investigate the effect of Fas (CD95) as well as ...FasL (CD95L) expression in primary malignant melanoma and melanoma metastases on overall survival (OS).
19 patients with metastatic malignant melanoma who were treated with different dacarbazine (DTIC)-based chemotherapy regimens were included in this study. From each patient, primary melanoma biopsies and biopsies from metastases were histologically evaluated. Immunohistology was performed with antibodies to Fas/CD95 and FasL/CD95L. Differences in OS were plotted using the Kaplan-Meier method and compared by the log rank test.
Fas/CD95 and FasL/CD95L expression was detected in 73.7 and 63.2% of primary melanomas, respectively. In metastases, expression of both Fas/CD95 (63.2%) and FasL/CD95L (47.4%) was markedly decreased. Presence of FasL/ CD95L expression in primary melanoma resulted in significantly (p = 0.024) prolonged OS compared with FasL/CD95L-negative high-risk primary melanomas. In contrast, loss of FasL/CD95L expression in melanoma metastases resected before chemotherapy was associated with significantly prolonged median survival (p = 0.0139).
Presence of FasL/CD95L expression in primary malignant melanoma and the loss of FasL/ CD95L expression in metastases seem to be positive prognostic factors.
Background: Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK).
Objectives: To investigate both the efficacy of different application times and the safety ...of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK.
Methods: Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded‐observer, parallel‐group study. After patch removal, study lesions were illuminated with red light (λem ≈ 630 nm; 37 J/cm2). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events.
Results: A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4‐h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2‐, 1‐ and 0.5‐h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4‐h application was identified as the ‘best treatment’. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range.
Conclusions: The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4‐h application.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Secreted lipases of
Candida albicans are encoded by a gene family with at least 10 members (
LIP1–
LIP10). The expression pattern of this multigene family was investigated using reverse transcription ...polymerase chain reaction in experimental infections and in samples of patients suffering from oral candidosis. The findings illustrate that individual lipase genes are differentially regulated in a mouse model of systemic candidosis with some members showing sustained expression and others being transiently expressed or even silent. The lipase gene expression profile depended on the stage of infection rather than on the organ localization. This temporal regulation of lipase gene expression was also detected in an experimental model of oral candidosis. Furthermore, the expression of candidal lipase genes in human specimens is shown for the first time.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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