Biomedical subjects
Publications and source records attributed to A Kuhn.
Basal cell carcinoma, the most common malignant neoplasm of the skin, has many clinical and histologic variants. We report about a 58-year-old patient with a rarely described, polypoid variant of this tumor. Polypoid basal cell carcinoma differs clinically from other variants by being exophytic and pedunculated and, histologically, the tumor aggregations are restricted only to the polypoid part.
We report about a 64-year-old patient who developed a verrucous squamous cell carcinoma in a long-standing hypertrophic lichen planus of the right lower leg. Neoplastic transformation of hypertrophic lichen planus has rarely been described in the literature.
Bullous systemic lupus erythematosus is a rare disease associated with subepidermal blistering and, in most cases, severe systemic manifestations. We describe a 19-year-old man with systemic lupus erythematosus who developed a bullous eruption along with a flare-up of systemic manifestations during the course of his disease and discuss the different forms of bullous lesions in patients with lupus erythematosus.
Primary cutaneous B cell lymphomas are rare malignant lymphoproliferative disorders of the skin. The prognosis is dependent on the clinical and histologic subtype; generally, these disorders show an indolent clinical course. We describe a 80-year-old woman with a large cutaneous B cell lymphoma of the lower leg. In contrast to other variants of cutaneous B cell lymphomas, this entity is characterized by an aggressive clinical course with an unfavorable prognosis. The mean survival rate is approximately 50%. This should be taken into account in the choice of treatment.
Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease is a non-Langerhans cell histiocytosis of unknown etiolosy. The most characteristic feature is lymphadenopathy, especially that of cervical lymph nodes. In approximately 40% of patients there are extranodal manifestations of the disease. Skin is the most commonly affected organ (27%). We report a 79-year-old female patient with purely cutaneous manifestations. This form of the disease is a very rare differential diagnosis in dermatology.
A 41-year old male patient presented with yellowish papules on the elbows, upper arms, back and the buttocks, as well as yellow streaks in the palmar creases. Laboratory examination revealed Fredrickson type IIb hyperlipidemia. Histologic changes were consistent with eruptive xanthomas. Treatment was started with HMG-CoA reductase inhibitors and dietary measures were taken to lower serum levels of cholesterol and triglycerides. Hyperlipidemia is the cause of eruptive xanthomas and strongly increases the risk of cardiovascular diseases.
Pityriasis rubra pilaris (PRP) is a rare papulosquamous disease with typical onset during the first and fifth decades. The skin disorder normally starts on the scalp and spreads caudally within a few weeks. It often results in a generalized erythroderma with sharply demarcated islands of sparing ("nappes claires"). A 65-year-old patient with severe PRP showed good clinial improvement after 8 months of treatment when treated with acitretin in combination with phototherapy and systemic gluocorticosteroids.
A 37-year-old patient presented with a generalized maculopapular rash, white oral plaques, and blurred vision of the left eye. Laboratory tests revealed the diagnosis of syphilis II and neurosyphilis in the context of HIV infection.
The expression of many cellular genes is modulated by DNA methylation and histone acetylation. These processes can influence malignant cell transformation and are also responsible for the silencing of DNA constructs introduced into mammalian cells for therapeutic or research purposes. As a better understanding of these biological processes may contribute to the development of novel cancer treatments and to study the complex mechanisms regulating gene silencing, we established a cellular system suitable to dissect the mechanisms regulating DNA methylation and histone acetylation. For this purpose, we stably transfected the neuroblastoma cell line U87 with a cytomegalovirus promoter-driven reporter gene construct whose expression was analyzed following treatment with the DNA methylation inhibitor 5'-aza-2'-deoxycytidine or histone deacetylation inhibitor trichostatin A. Both substances reactivated the silenced cytomegalovirus promoter, but with different reaction kinetics. Furthermore, whereas the kinetics of reactivation by trichostatin A did not substantially change over the time range considered (5 days), reactivation induced by 5'-aza-2'-deoxycytidine showed profound differences between day 1 and longer time points. We showed that this effect is related to the down-regulation of DNA replication by 5'-aza-2'-deoxycytidine. Finally, we have shown that the simultaneous administration of trichostatin A and 5'-aza-2'-deoxycytidine results in reactivation of the CMV promoter according to a cooperative, not synergistic or additive, mechanism. In conclusion, our cellular system should represent a powerful tool to investigate the complex mechanisms regulating gene silencing and to identify new anticancer drugs.
Immunocompromised patients are developing in an increasing frequency acyclovir-resistant herpes simplex infections. Different treatment options need to be evaluated considering the possible side effects in regard to the patients' immunocompromised status. A 73-year-old woman with B-cell lymphatic leukemia with a secondary antibody deficiency syndrome and anemia suffered for one year with perianal ulcerations caused by acyclovir-resistant herpes simplex infection Type II. Based on previous reports about successful treatment of acyclovir-resistant herpes simplex infections with foscarnet, cidofovir or vidarabine and considering the different side effects of these drugs as well as the underlying diseases of the patient, we treated her with foscarnet intravenously. After 3 months the ulcers showed a nearly complete remission.
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Isolating and analyzing interstitial water (IW) during sediment toxicity tests enables researchers to relate concentrations of contaminants to responses of organisms, particularly when IW is a primary route of exposure to bioavailable contaminants by benthic dwelling organisms. We evaluate here the precision of sampling IW with the dialysis or 'peeper' method using sediments spiked with five different concentrations of cadmium. This method is one of several that are commonly used for collecting IW. Seven consecutive ten-day toxicity tests were conducted on these sediments and IW samples were collected at the end of each of these tests. Prior to each test initiation and insertion of IW samplers, sediments were allowed to equilibrate for seven days under flow-through conditions with filtered seawater. At the end of each ten-day testing period, peepers were retrieved, and IW cadmium measured. Data sets were organized by treatment and test number. Coefficients of variation (CV) for the six replicates for each sediment and testing period and for each sediment across testing periods (42 replicates) was used as a measure of sampling precision. CVs ranged from 25 to 206% when individual testing periods were considered, but ranged from 39 to 104% when concentrations for all testing periods were combined. However, after removal of outliers using Dixon's Criteria, the CVs improved and ranged from 6 to 88%. These levels of variability are comparable to those reported by others. The variability shown is partially explained by artifacts associated with the dialysis procedure, primarily sample contamination. Further experiments were conducted that support our hypothesis that contamination of the peeper causes much of the variability observed. If method artifacts, especially contamination, are avoided the dialysis procedure can be a more effective means for sampling IW metal.
Toxicity Identification Evaluations (TIEs) can be used to determine the specific toxicant(s), including ammonia, causing toxicity observed in marine sediments. Two primary TIE manipulations are available for characterizing and identifying ammonia in marine sediments: Ulva lactuca addition and zeolite addition. In this study, we compared the efficacy of these methods to (1) remove NH(x) and NH(3) from overlying and interstitial waters and (2) reduce toxicity to the amphipod Ampelisca abdita and mysid Americamysis bahia using both spiked and environmentally contaminated sediments. The utility of aeration for removing NH(x) and NH(3) during a marine sediment TIE was also evaluated preliminarily. In general, the U. lactuca and zeolite addition methods performed similarly well at removing spiked NH(x) and NH(3) from overlying and interstitial waters compared to an unmanipulated sediment. Toxicity to the amphipod was reduced approximately the same by both methods. However, toxicity to the mysid was most effectively reduced by the U. lactuca addition indicating this method functions best with epibenthic species exposed to ammonia in the water column. Aeration removed NH(x) and NH(3) from seawater when the pH was adjusted to 10; however, very little ammonia was removed at ambient pHs ( approximately 8.0). This comparison demonstrates both U. lactuca and zeolite addition methods are effective TIE tools for reducing the concentrations and toxicity of ammonia in whole sediment toxicity tests.
We propose a novel approach, which allows the control of the spatial arrangement of redox mediator, coenzyme and enzyme on the electrode at a molecular level, using essentially electrostatic interactions. The first step consists of adsorbing a monolayer of molecules out of a new family of redox mediators, substituted nitrofluorenones. In a second step, a monolayer of calcium cations is immobilized at the interface. It serves as a bridge between the redox mediator and the subsequently adsorbed coenzyme. The weak interaction between a carboxyl group of the redox mediator and the coenzyme's phosphate groups, revealed by QCM measurements, allows the coenzyme to keep its natural activity in the adsorbed state. In the last step, we use the intrinsic affinity of this monolayer of NAD(+) for dehydrogenases to build up a supramolecular sandwich composed of mediator/Ca(2+)/NAD(+)/dehydrogenase. This simple modification procedure, which might constitute a versatile approach for the low cost assembly of well-defined biosensors surfaces, has been successfully applied to the enzymatic detection of glucose, glutamate and alcohol.
Carbon paste electrodes were modified with a nitrofluorenone derivative, 2,4,7-trinitro-9-fluorenone, adsorbed on zirconium phosphate (ZP). After electrochemical reduction of the fluorenone derivative, it turns into a very efficient mediator for electrocatalytic NADH oxidation, with a formal potential of about +250 mV vs. Ag/AgCl. The electrochemistry and the electrocatalytic properties of the mediator were investigated with cyclic voltammetry and rotating disk electrode methodology. The second order rate constant with NADH was evaluated and found to be higher than 10(6) M(-1) s(-1), thus approaching true diffusion controlled currents for NADH oxidation.
Restenosis post angioplasty remains the major limitation of several therapeutic interventions including stent implantation. This explains the ongoing interest in its basic pathogenic mechanisms and factors. The aim of the present study was to assess the localization and maximal expression of Bcl-2, a central antiapoptotic protooncogene, and of heat shock protein 47 (HSP47), a marker of early collagen synthesis, in the context with hyperplastic neointima formation as well as concomitant transmural remodeling processes following angioplasty. 0, 4, 24 and 48 hours, 4, 7 and 14 days post balloon traumatization by use of a rat carotid artery model, specific vascular wall compartments were evaluated concerning area, cell density as well as Bcl-2 and HSP47 expression by immunohistochemistry and morphometry, supplemented by electron microscopy (TEM). Neointimal cell accumulation was detected 4 days post angioplasty, characterized by luminal cells adherent to the internal elastic lamina, associated with maximal Bcl-2 and HSP47 expression amounting to 49% and 41%, respectively. With ongoing neointimal formation, a luminal prevalence of both key determinants and a decreasing expression in basal neointimal areas were found. In the media, a temporally reduced cell density was observed significant at 48 hours post trauma. Constitutive HSP47 expression of the media was constant during the entire observation period, whereas sparse Bcl-2 signalling was induced post angioplasty maximal on day 2 with 3% and on day 14 with 5%. The adventitia demonstrated a transient structural separation between day 4 and 7, exhibiting an inner layer with sparse cellularity and an outer layer with extremely high cell density as well as pronounced neovascularization. In this outer adventitia layer, a high frequency of signals for both Bcl-2 and HSP47 were observed amounting to 29% and 57%, respectively. Complementary TEM analysis gave no evidence of transmural migratory events propagated by adventitial cells and thereby supports early neointimal formation by luminal cell recruitment and marked co-expression of anti-apoptotic Bcl-2 and matrix-generating HSP47 as important survival factors. Clinical implications of these findings may be seen in the integration of proapoptotic substances with temporal efficacy in order to prevent restenosis, e.g., by use of coated stents.
BACKGROUND: Lupus erythematosus tumidus (LET), a photosensitive skin disorder with characteristic clinical and histological features, has not been generally accepted as a subset of cutaneous lupus erythematosus (CLE). OBJECTIVES: To analyse the expression of epidermal surface molecules in skin biopsy specimens from patients with LET and to relate the results to other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute CLE (SCLE). METHODS: In total, 45 patients with different subtypes of CLE were included in the study, and cryostat sections from primary and ultraviolet (UV) A- and UVB-induced skin lesions were investigated using immunohistochemical methods. RESULTS: In contrast to healthy controls, skin lesions of LET showed upregulation of intercellular adhesion molecule-1 (ICAM-1) and histocompatibility class II molecules (HLA-DR), with an expression pattern resembling that seen in DLE and SCLE. Furthermore, staining with a monoclonal antibody against 27E10, a distinct marker for cell activation and differentiation, revealed intense focal or band-like labelling of all epidermal layers independent of the type of lesion. CONCLUSIONS: Expression of epidermal surface molecules such as ICAM-1, HLA-DR and 27E10 is equally upregulated in primary and UV-induced lesions of patients with LET, DLE and SCLE. These results support our recent clinical findings that LET represents a distinct subset of CLE with a similar immunopathomechanism rather than a different disease.