Biomedical subjects
Publications and source records attributed to Jürgen Bauer.
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Most melanocytic nevi develop on sun-exposed skin during childhood and adolescence and commonly harbor BRAF mutations or, less frequently, NRAS mutations. A small subset of nevi is present at birth, and therefore must develop independently of UV light. To assess whether these nevi have a different mutation spectrum than those that develop on sun-exposed skin, we determined the BRAF and NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10 (70%) proliferating nodules that developed early in life in congenital nevi showed mutations in NRAS. A separate set of nevi that displayed histological features frequently found in nevi present at birth ("congenital pattern nevi") but lacked a definitive history of presence at birth showed an inverse mutation pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically distinct from those that develop later, and histopathologic criteria alone are unable to reliably distinguish the two groups. The results are consistent with the finding in melanoma that BRAF mutations are uncommon in neoplasms that develop in the absence of sun-exposure.
Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.
Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells of the immune system with the unique ability to initiate and maintain primary immune responses. In order to better characterize the functional and phenotypic features of DCs, a subtractive cDNA library to identify differentially expressed genes in monocyte-derived DCs (MDCs) was constructed. Using this approach, we found that the epithelial transcription factor ESE-3, which was previously shown to be exclusively expressed in cells of epithelial origin, is differentially expressed in MDCs. This was further confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses. The expression of ESE-3 is up-regulated upon maturation of MDCs and inhibited by treating the cells with IL-10 or IFN-gamma. Knockdown experiments using siRNA suggest that ESE-3 plays an important role during MDC development. Our results might help to improve the phenotypic characterization of DCs and lead to a better understanding of the cellular mechanisms involved in antigen presentation and T-cell stimulation.
Sunscreens have been proposed as protective measures to inhibit the development of melanocytic nevi in childhood and to decrease the long term risk for cutaneous melanoma development. Our present study investigates the influence of sunscreen use and education on the number of incident melanocytic nevi. A total of 1,812 children in 78 public nursery schools in 2 German cities were randomized to 3 study arms: (i) parents were informed on study purpose and sun protection measures only at an initial educational meeting; (ii) parents received educational material 3 times yearly; and (iii) education and 800 ml free broad spectrum sunscreens with sun protection factor 25 provided on a yearly basis. Final assessment after 3 years follow-up included 1,232 children (68%). Changes of sun protection habits including sunscreen use were sparse, without any differences attributable to the intervention efforts. As a consequence, there were no significant differences between the 3 study arms for the main outcome measure, the number of incident melanocytic nevi. Analysis of the sunscreen use in the entire cohort irrespective of our study arms did not show any impact on incident nevus numbers in bivariate or multivariate analysis. In conclusion, intervention with educational letters and free sunscreens seemingly had no additional effect on sun-protection for German children. High prevalence of sunscreen use at study commencement, social desirability, and inadequate application of sunscreens might have partially covered their effect.
Ventricular septal defects (VSDs) complicate the arterial switch operation (ASO) in newborns with transposition of the great arteries because of prolonged cardiac arrest time and subsequent ventricular dysfunction. Three newborns with paramembranous VSDs were successfully treated using the newly designed Amplatzer membranous VSD occluder during the ASO. The implantation of a 4-mm asymmetric Amplatzer device in 2 patients and an 8-mm device in the third resulted in the complete occlusion of the septal defects. The cardiac arrest time for anatomic repair might be effectively reduced by this new approach in pediatric cardiac surgery.
The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic-moderate and intermittent-high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3-year follow-up was conducted in 1,232 young children 2-7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun-protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent-high sun exposure during holidays (p < 0.001) and chronic-moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic-moderate or intermittent-high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts.
The number of melanocytic nevi is the most important risk factor for cutaneous melanoma. This 1998 cross-sectional study of 1,812 children aged 2-7 years from 78 day-care centers in Germany analyzed the protective effect of sunscreen and clothing on the number of melanocytic nevi. Total body nevi were counted, and pigmentary features were assessed. Parents underwent a standardized interview concerning their children's sun exposure and sun-protective behavior. Almost 95% of the children had used sunscreen previously. Children who used sunscreen and wore more clothing spent significantly longer periods on holidays in sunny climates (p < 0.001 and p = 0.006, respectively) and had a higher outdoor activity score at home (p < 0.001 and p = 0.012, respectively). Multivariate analysis adjusted for confounders showed no significant protective effects of applying sunscreen. Examination of the potential protective effect of clothing revealed an inverse dose-response correlation between the number of clothes worn at the beach or outdoor swimming pool and the number of melanocytic nevi (p < 0.001, adjusted for confounding). Randomized controlled trials are needed to confirm these results. Meanwhile, public education should aim to protect children primarily by sun avoidance and protective clothing, while sunscreen should also be used.
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We report the case of a 70-year-old white male with an extensive recurrence of lentigo maligna in a skin-transplanted region. He was treated with imiquimod 5% cream topically applied 5 times a week for a total duration of 9 months. Clinically and histologically, a complete clearing of the lesion was observed after treatment. Topical treatment with imiquimod seems to be effective and safe in lentigo maligna.
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OBJECTIVE: To evaluate testicular function in men with epilepsy treated with different antiepileptic drugs (AED) vs no drugs. METHODS: Two hundred men with epilepsy (mean age 36 years) were investigated. Inclusion criteria included one or no AED, no co-medication, and no endocrine co-morbidity. Findings were compared with those from 105 healthy men (mean age 33.9 years). Luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), free testosterone (free T), and inhibin B were measured. RESULTS: One hundred seventy-eight men had focal epilepsy (117 of these had temporal lobe epilepsy [TLE]) and 22 idiopathic generalized epilepsy (IGE). Thirty-three men were not on AED; 124 men received enzyme-inducing AED. Free T was lowered in all patient subgroups, and the T/LH ratio was lowered in all groups except patients with IGE and patients receiving valproate (VPA). T was lower in patients with temporal than extratemporal focal epilepsy. Compared with TLE patients on carbamazepine (CBZ), patients treated with VPA had higher total T and lower LH values, resulting in a significantly lower T/LH ratio with CBZ. CONCLUSIONS: Epilepsy, especially TLE, adversely affects testicular endocrine function. CBZ may increase the negative effects of epilepsy on serum levels of reproductive hormones.
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Explore the source record for details and available documents.