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Biomedical subjects

M Landthaler

Publications and source records attributed to M Landthaler.

At least 109 records · Page 6Linked to original sources

Teledermatology--the requirements of dermatologists in private practice.

Eighty-four dermatologists in private practice in Bavaria were surveyed by postal questionnaire. Of the 45 who responded (a 54% response rate), 96% used a computer in their private practice. Fifty-seven per cent of respondents owned systems with Pentium processors, while 23% were still using 386 or 486 processors. Most of them used the Windows 95, UNIX or Apple operating system. Of the respondents who had a modem, 74% used ISDN. There were few modems connected to the ordinary telephone network. Of all respondents, 56% used email regularly. Several possible teledermatology applications were proposed in the survey (i.e. teleconsultation, on-line/off-line videoconferencing, email attachments). Fifty-six per cent of respondents said that they would perform teleconsultations with dermatology clinics, 40% preferred a teleconsultation via telephone and computer, and 42% sending files via email. The survey demonstrated that a high proportion of dermatologists in private practice would use a teledermatology service.

Adult↗

Detection of activated complement complex C5b-9 and complement receptor C5a in skin biopsies of patients with systemic sclerosis (scleroderma).

OBJECTIVE: Upregulated matrix synthesis is a hallmark of systemic sclerosis (SSc). There are indications that growth factors such as platelet derived growth factor (PDGF) are involved in proliferative pathways in SSc lesions. As activated complement releases PDGF from endothelial cells, we searched for activated complement and the complement receptor for C5a (C5aR) in skin biopsies of patients with SSc. METHODS: Snap frozen sections of 8 patients with early SSc and 5 patients with longterm SSc were examined. Using monoclonal antibodies against activated complement complex C5b-9 and the C5aR, skin biopsies derived from both clinically involved and non-involved skin were examined by APAAP immunohistochemistry. RESULTS: A pattern of activated complement C5b-9 and the CSaR could be detected in SSc microvasculature. Eleven of the 13 patients (7/8 patients with early SSc) showed positive staining for C5b-9. The CSaR was detected in 6 of the 8 patients with early SSc. In 3 patients with longterm disease, C5aR expression could also be detected in non-involved skin. CONCLUSION: Activated complement and complement receptors could be detected in early and late stages of SSc skin lesions. The presence of complement receptors in non-involved skin may indicate preclinical activation of pathways resulting in growth factor dependent matrix synthesis.

Antigens, CD↗

Unexpected abundance of self-splicing introns in the genome of bacteriophage Twort: introns in multiple genes, a single gene with three introns, and exon skipping by group I ribozymes.

Analysis of RNA that can be labeled with GTP indicates the existence of group I introns in genes of at least three transcriptional classes in the genome of Staphylococcus aureus bacteriophage Twort. A single ORF of 142 amino acids (Orf142) is interrupted by three self-splicing group I introns, providing the first example of a phage gene with multiple intron insertions. Twort Orf142 is encoded in a message that is abundant 15-20 min after infection and is highly similar to a late gene product (Orf8) of the morphologically related Listeria phage A511. The introns in orf142 are spliced in vivo and contain all the conserved features of primary sequence and secondary structure of group I introns in subgroup IA2, which includes the introns in Escherichia coli phage T4 and the Bacillus phages beta22 and SPO1. Introns I2 and I3 in orf142 are highly similar, and their intron insertion sites are closely spaced. The presence of transcripts with a skipped exon between these introns indicates that they may fold into a single active ribozyme resulting in alternative splicing. Alternatively, the cleaved 5' exon preceding I2 may undergo trans splicing to the 3' exon that follows I3. Regardless of the detailed mechanism, these results demonstrate a new means whereby a single gene can give rise to multiple messenger RNAs.

Amino Acid Sequence↗

Long-pulse dye laser for photodynamic therapy: investigations in vitro and in vivo.

BACKGROUND AND OBJECTIVE: Continuous wave lasers or incoherent lamps are used effectively for photodynamic therapy (PDT). As the mechanism of action of pulsed lasers in PDT is not known, we investigated the efficacy of PDT with 5-aminolevulinic acid (ALA) using a long-pulse (1.5 ms) tunable flashlamp-pumped pulsed dye laser (LPDL) in vitro and in vivo. STUDY DESIGN/MATERIALS AND METHODS: HaCaT human keratinocytes were incubated with ALA (3 mmol/l) and irradiated (0-50 J/cm(2)) using the LPDL at 585 nm, 595 nm, or 600 nm vs. an incoherent light source (580-740 nm). Topical ALA-PDT was performed on 24 patients with actinic keratoses (AK) on the head (n = 200) after incubation with a 20% ALA emulsion and irradiation by either an incoherent light source (160 mW/cm(2), 60-160 J/cm(2)) or the LPDL (585 nm, 18 J/cm(2)). RESULTS: Maximal cytotoxic effects in vitro were achieved using the LPDL at 585 nm or the incoherent lamp (50 J/cm(2)). Sodium azide, a quencher of singlet oxygen, significantly reduced cell killing, suggesting that the cytotoxic effects are mainly mediated by singlet oxygen. This is supported by an increase of lipid peroxides as determined by malondialdehyde after adding D(2)O. Complete remission was achieved in 79% of 100 AK treated by ALA and the LPDL and in 84% of 100 AK treated by ALA and the incoherent lamp. Pain during light treatment was significantly reduced by using the LPDL. Control lesions (LPDL without ALA) did not clear. CONCLUSION: These results show the in vitro and in vivo efficacy of ALA-PDT using a pulsed light source mediated by singlet oxygen.

Adolescent↗

In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancers.

Elevated levels of melanoma-inhibiting activity (MIA) were measured previously in the serum of patients with metastasized melanomas and in a subgroup of patients with advanced-stage breast cancers. This study aimed therefore to visualize in situ expression patterns of MIA protein and mRNA in melanomas and breast cancers by means of immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. Analysis of a panel of seven common melanocytic naevi, ten cutaneous melanomas, and 12 melanoma metastases detected high levels of both mRNA and protein in all melanomas and metastases, but only very low mRNA levels in three of seven naevi. Compared with the expression of pMel (HMB-45), tyrosine, and S-100 in these tumours, these results show that MIA provides a novel and sensitive marker for neoplastic melanocytes. Expression was not detected in other skin tumours including basal cell cancers and squamous cell cancers, nor in normal melanocytes and keratinocytes. MIA expression in adenocarcinomas was further studied in a panel of 20 specimens obtained from 16 advanced-stage breast cancers and four metastases. Significant levels of mRNA were detected in 17 of the 20 specimens and low levels in the other three tumours. Immunostaining visualized specific protein expression in the tumour cells of all 20 cancer specimens. These investigations define for the first time in situ expression patterns of MIA in melanomas and breast cancers and suggest a much broader expression in malignant epithelial neoplasms than previously determined by serum studies.

Adenocarcinoma↗

[Ofuji papuloerythroderma: PUVA bath treatment].

Papuloerythroderma of Ofuji is a rare skin disorder described primarily in Japanese patients. It occurs primarily in elderly men. The initial lesions are diffuse red papules, sparing the face, palms and soles. Later the papules coalesce into an erythroderma, with typical sparing of the skin folds and creases (the deck chair sign). Pruritus is usually intense. Lymphadenopathy, peripheral blood eosinophilia and elevated IgE levels all are common. Both systemic corticosteroids and systemic PUVA therapy have been recommended. We describe a German male who fulfilled the diagnostic criteria for papuloerythroderma of Ofuji and responded well to PUVA bath therapy with both improvement in skin findings and reduction in pruritus.

Aged↗

[Therapy-resistant pyoderma gangrenosum--treatment with mycophenolate mofetil and cyclosporine A].

A 68-year old woman presented with ulcerations on the calves that had occurred spontaneously. The very painful lesions both clinically and histologically showed the characteristics of pyoderma gangrenosum. During hospitalization she was treated with corticosteroids (oral, i.v., topically), clofazimine, cyclophosphamide, intravenous immune globulin, cyclosporine (oral, local), dapsone, thalidomide and sodium cromoglycate (topically) without any benefit. Finally, when treated with mycophenolate mofetil (CellCept) (oral) and cyclosporine (oral), her skin lesions showed continuous improvement. The topical application of thrombocytic growth factors (cytokines) probably accelerated the granulation. Eight weeks after initiating this treatment the lesions could be covered with split thickness skin grafts. Our observation suggests that mycophenolate mofetil, a novel immunosuppressive agent which has thus far been used almost exclusively in transplantation medicine, may be an effective therapeutic modality in combination with cyclosporine A for the treatment of pyoderma gangrenosum.

Aged↗

[Porokeratosis Mibelli gigantea: case report and literature review].

Porokeratos of Mibelli is a rare inherited disorder of epidermal keratinization, whose pathogenesis is not fully understood. The common clinical feature is a erythematous plaque surrounded by a hyperkeratotic border. The histopathologic hallmark is a parakeratotic cornoid lamella. An unusual case of porokeratosis gigantea, a morphological variant of classical porokeratosis of Mibelli, is reported. The pathogenesis, taking in account especially the clonal hypothesis and premalignant nature of porokeratosis, is discussed.

Acitretin↗

[CO(2) laser vaporisation of actinic cheilitis].

As a premalignant condition, actinic cheilitis requires therapy, and multiple treatment modalities have been described. Although frequently reported in Angloamerican literature, CO(2) laser vaporization for the treatment of actinic cheilitis is scarcely mentioned in German journals. We report 19 cases of CO(2) laser treatment of actinic cheilitis. In only one case, the ablation proved to be too superficial after the first treatment. Except in this case we did not see any recurrences and only one case with minor scarring within a median follow up period of 16 months. In comparison with other treatment modalities, we consider the CO(2) laser ablation to be a safe and cost-saving method with excellent cosmetic results.

Adult↗

Expression of RANTES in biopsies of skin and upper gastrointestinal tract from patients with systemic sclerosis.

Inflammatory infiltrates and upregulated collagen production are hallmarks of systemic sclerosis (SSc). There are indications that chemokines are involved in accumulation of inflammatory and matrix-synthesizing cells in SSc skin lesions. Therefore, we searched for the expression and localization of the chemokine RANTES ("regulated upon activation and normal T cells expressed and secreted") in skin and esophageal biopsies from patients with SSc. Using immunohistochemistry and in situ hybridization, skin biopsies derived from clinically involved and noninvolved skin of 18 patients with early and long-term SSc were examined for RANTES expression and compared with nondiseased skin sections of seven patients without SSc. In addition, esophageal snap biopsies were taken in a subgroup of six SSc patients. Strong expression of RANTES could be detected in the epidermis in keratinocytes of patients with short-term and long-term disease, both on the mRNA and protein level. The percentage of RANTES-expressing cells were significantly higher in clinically noninvolved skin sections than in involved skin areas. In contrast, no RANTES expression was found in esophageal biopsies or in the control group. The results indicate that RANTES is present in human sclerodermatous skin. RANTES may be involved in early pathogenesis of SSc as well as in fibrosis pathways, either by chemoattraction of immunocompetent cells and/or by modulation of collagen production.

Adult↗

Assessment of microsatellite instability and loss of heterozygosity in sporadic keratoacanthomas.

Variations in the length of simple repetitive tandem repeats (microsatellite instability, MIN) between constitutive and tumour DNA, which is characteristic of tumours in patients affected with hereditary nonpolyposis colon cancer (HNPCC), have been found to be very important in the carcinogenesis of a variety of human neoplasms. Recently, MIN has been found in sebaceous and colorectal tumours as well as in keratoacanthomas of Muir-Torre syndrome. In order to elucidate the significance of both MIN and loss of heterozygosity (LOH) in the pathogenesis of sporadic keratoacanthomas, the presence of MIN and LOH at five loci [chromosome 5q21 (D5S346, APC), 9p21 (D9S171, p16), 10pter (D10S89, Mfd28), 11p (D11S904) and 17p12 (D17S520, p53)] was evaluated. MIN was found at only one locus (p53) in 1 of 12 keratoacanthomas and no evidence for the presence of LOH could be detected. Our results suggest that, in contrast to keratoacanthomas associated with Muir-Torre syndrome, neither MIN nor LOH appear to be significant in the induction of sporadic keratoacanthomas.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

Photosensitization of human skin cell lines by ATMPn (9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene) in vitro: mechanism of action.

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a promising new photosensitizer characterized by high absorption around 640 nm and high singlet oxygen yield. To study the mechanism of action in vitro we have investigated uptake, intracellular localization, cell survival and ultrastructural changes following photodynamic treatment in human cell lines derived from the skin (SCL1 and SCL2, squamous cell carcinoma; HaCaT keratinocytes; N1 fibroblasts). Using flow cytometry we have determined the cellular fluorescence as a marker for the uptake of ATMPn after incubation for 60 min. Co-staining with ATMPn and fluorescent dyes specific for cell organelles reveals an intracellular localization of ATMPn in lysosomes. Following irradiation using an incoherent light source (580-740 nm) and a light fluence of 24 J cm-2, phototoxicity is determined by means of the 3-4.5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay. For all cell lines ATMPn concentrations above 15 nM yield a significant phototoxic effect. The 50% effective concentration, EC50, for SCL1 cells is 11.2 +/- 2.9 nM ATMPn. ATMPn uptake and phototoxicity are more effective for HaCaT and SCL1 as compared to SCL2 and N1 cells. Growth curves confirmed the results of the MTT assay. Because of the high lysosomal accumulation of ATMPn, already low photosensitizer concentrations without dark toxicity yield a high photodynamic effect. Immunofluorescence and electron microscopy reveal damage to tonofilaments, plasma membrane and mitochondria, indicating a mechanism unrelated to apoptosis. A dose yielding complete cell killing, as needed for oncological indications, might lead to necrosis, whereas lower sub-lethal doses result in induction of apoptosis.

Cell Line↗