Biomedical subjects
Publications and source records attributed to M Landthaler.
We compared a cw carbon dioxide flash-scanning laser system to an Er:YAG laser in laser skin resurfacing of facial rhytides. In all patients, CO2 laser treatment showed a better cosmetic result whereas erythema and postinflammatory hyperpigmentation were less marked in Er:YAG laser therapy.
A new flashlamp-pumped pulsed dye laser with 1.5 ms pulse length and tunable wavelengths between 585 and 600 nm (Candela ScleroPLUS) is now available for the treatment of ectatic leg veins. We evaluated 232 single test treatments using 595 and 600 nm wavelength in 75 test persons. For smaller vessels up to a diameter of 0.5 mm, treatments at 16 and 18 J/cm2 showed good results in 60 and 82% respectively; for vessels up to 1 mm in 27 and 33%. Treatment at 595 nm was a little more effective than at 600 nm. Larger vessels could not be treated effectively. The main side effects consisted in hyper-(34%) or hypopigmentation (30%). Thus, in addition to the usual sclerotherapy, this laser is a useful device for the treatment of leg vein ectasia.
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The protein MIA was identified and isolated from the tissue culture supernatant of melanoma cells in vitro by its ability to inhibit thymidine incorporation by melanoma cell lines. After purification and partial sequencing of the peptide, a fragment of the MIA cDNA was cloned by RT-PCR. This cDNA fragment was used to screen phage libraries and subsequently fully encoding human and murine MIA cDNA and genomic DNA clones were obtained. The MIA gene spans a region of approximately 2 kb and is divided into 4 exons. Mapping the MIA gene revealed that the human gene is located on chromosome 19 and the murine gene on chromosome 7. The MIA open reading frame spans 131 (human) or 130 (murine) amino acids. The first 24 (human) or 23 (murine) amino acids represent a signal sequence directing the secretion of MIA into the extracellular compartment. The mature, secreted MIA consists of 107 amino acids and its MW is approximately 11 kDa. Preliminary structural data suggests that MIA is a small globular protein stabilized by two intramolecular disulfide bonds. Expression studies of protein und mRNA levels indicate that MIA is expressed specifically by malignant melanoma cells and chondrocytes. This points to a highly restricted expression pattern which is controlled by the MIA promoter. In addition, MIA provides a clinically useful parameter in patients with malignant melanoma. Enhanced values were measured in the serum of all patients with metastatic melanoma (stage III and IV). In vitro and in vivo experiments using recombinant MIA protein revealed that MIA specifically inhibits attachment of melanoma cells to fibronectin and laminin. Further analysis indicated a direct binding between MIA and the matrix proteins. This finding provides an explanation for the capability of MIA to inhibit proliferation of melanoma cells in vitro. Our studies suggest a putative function of MIA in regulated detachment of melanoma cells from the extracellular matrix which is an important step in metastasis.
The knowledge of the exact time course of a photosensitizer in tumour and surrounding host tissue is fundamental for effective photodynamic therapy (PDT) and fluorescence-based diagnosis. In this study the time course of porphyrin fluorescence following topical application of 5-aminolaevulinic acid (ALA) using different formulations, concentrations and incubation times has been measured in amelanotic melanomas (A-Mel-3) (n = 54) grown in transparent dorsal skinfold chambers of Syrian golden hamsters and in human basal cell carcinomas (BCCs) (n = 40) in vivo. To simulate the accumulation of ALA-induced protoporphyrin IX (Pp IX), a three-compartment model has been developed and rate constants have been determined. The kinetics of both the A-Mel-3 tumours and the BCCs show a significantly higher fluorescence intensity in tumour as compared to normal surrounding host tissue. Maximal fluorescence intensity in A-Mel-3 tumours as a percentage of the reference standard used occurs 150 min post incubation (p.i.) using a 1, 3 or 10% (vol.) ALA solution buffered to pH 7.4 and 1 h incubation time. After a 4 h incubation time maximal fluorescence intensity in tumour is measured shortly p.i. A concentration of 10% ALA does not increase the fluorescence intensity as compared to 3% ALA following 4 h incubation, but either 3 or 10% ALA yields a significantly higher fluorescence after 4 h incubation time as compared to 1 h. The fluorescence intensity following an 8 h incubation reaches its maximum directly p.i. for all concentrations and then decreases exponentially. The fluorescence intensity in the surrounding host tissue shows no statistically significant difference regarding concentration or incubation time. At least during the first hour p.i., the fluorescence intensity measured in the surrounding tissue is lower as compared to that in the tumour in all groups. 24 h after topical application hardly any fluorescence is detectable in tumour or surrounding host tissue in all experimental groups. Incubating human BCCs with a 20% ALA cream (water-in-oil emulsion) or a 20% ALA gel (containing 40% dimethyl sulfoxide) for approximately 2 h yields a similar fluorescence intensity directly after incubation for either cream or gel. However, while yielding a maximum 120 min p.i. with cream, the fluorescence intensity increases for a longer time (about 2-3 h p.i.) and up to higher values using the gel formulation. In surrounding normal skin, cream as well as gel formulation yields a similar fluorescence intensity directly after incubation. Afterwards the fluorescence intensity decreases slowly using the cream whereas a further increase of the fluorescence intensity is measured in the normal skin with a maximum 240 min p.i. using the gel formulation. The results of the proposed three-compartment model indicate that the observed selectivity of accumulated porphyrins following topical application of ALA is mainly governed by an increased ALA penetration of the stratum corneum of the skin, an accelerated ALA uptake into the cell and a higher porphyrin formation in tumour as compared to normal skin tissue, but not by a reduced ferrocheletase activity.
The photo-fading of the S0-S1 absorption band of the infrared dye indocyanine green sodium iodide (ICG-NaI) has been studied by cw laser excitation to the S1 band. Monomeric solutions in water, heavy water, aqueous sodium azide, human plasma, methanol and dimethyl sulfoxide (DMSO) as well as J-aggregated solutions in H2O and D2O have been investigated. A leucoform of indocyanine green seems to be formed by photodegradation. The degradation slows down with exposure time. The initial degradation yield, phi D,0, is determined. In monomeric and dimeric water, heavy water and sodium azide solutions the initial photostability is of the order of phi D.0 approximately 10(-3), in the organic solvents methanol and DMSO it is of the order of phi D.0 approximately 10(-5), and in human plasma it is phi D.0 approximately 2 x 10(-6). J-aggregates at high concentration are very stable. The thermal stability of the ICG-NaI solutions at room temperature in the dark is compared with their photostability. The thermal degradation time of monomeric and dimeric ICG-NaI in water, heavy water and sodium azide solutions is t(th) approximately 10 days, while no thermal degradation is observed for ICG-NaI J-aggregates and ICG-NaI in methanol, DMSO and human plasma.
Indocyanine green (ICG) is clinically approved for the determination of liver function, cardiac output and plasma volume. In this pilot study, ICG was used as photosensitizer in combination with a diode laser to treat AIDS-associated Kaposi's sarcoma (KS) in three patients. Directly and up to 50 min after intravenous administration of ICG (2-4 mg kg(-1) body weight), KS (n=57), mainly plaque-type, were irradiated using a diode laser (lambda em=805 nm, 100 J cm[-2], 0.5-5 W cm[-2]) matching the absorption maximum. Complete remission of KS (n=16) was achieved when irradiated 1-30 min after injection of the second dose of ICG (2 x 2 mg kg(-1) b.w., 30 min apart) with 3-5 W cm(-2) and 100 J cm(-2). Biopsies (n=3) revealed necrosis of the tumour 24 h and complete remission 4 weeks after therapy. In general, systemic side-effects were not observed and cosmetic results were very good. However, hyperpigmentation occurred temporarily in lesions located on the lower extremities. These findings show that AIDS-associated KS can be effectively treated after photosensitization with ICG and subsequent irradiation with an appropriate diode laser. However, additional investigations need to elucidate the exact mechanism of action of ICG-mediated phototherapy and have to show the efficacy for the treatment of other highly vascularized solid tumours.
This study was designed to evaluate the effect of selective photothermolysis on dark pigmented hair follicles treated with a normal-mode ruby laser (694-nm wavelength, pulse duration 0.5 ms, fluence 20 J/cm2, spot size 2 mm). In 15 volunteers, four test areas each were selected. After shaving, the first area was irradiated once, the second twice, the third three times and the fourth served as control area. A punch biopsy was taken from each volunteer immediately after the first laser treatment. Four weeks after the last irradiation, no effect was found in six cases and little effect in another six cases (50-90% regrowth). Hair regrowth of less than 30% was observed in only three cases. Eight weeks after the last session, no effect was found in 11 cases, little effect in 2 cases (10%) and less than 30% regrowth in only 2 cases. Twelve weeks after the last treatment, no difference could be detected between the areas untreated and treated by laser. The laser parameters applied in this study do not result in effective epilation of body hair. In some cases, a delay in growth of several weeks was noticed.
This is the first case in the literature describing naevi spili, café-au-lait spots and melanocytic naevi aggregated along-side Blaschko's lines. The pattern of melanocytic lesions in our patient is different from the congenital pigmentary syndromes and the segmental distribution of melanocytic naevi, the quadrant distribution of dysplastic naevi or the partial unilateral lentiginosis which here are shortly reviewed. The distribution may be a result of a somatic mutation occurring at an early stage of embryogenesis when neural structures had already been formed.
Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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We report a case of a congenital nevus sebaceus with numerous brown macules and papules in the left auricular region. In the same lesion, pigmented basal cell carcinomas developed later in life. Additionally, on the left side of the neck, both shoulders and the left arm, features of nevus spilus with melanocytic and blue nevi were present. Such a combination of nevus sebaceus with melanocytic lesions may be explained by the concept of twin spotting and represent another case of phacomatosis pigmentokeratotica.
The Lerks, ligands of eph-related receptor tyrosine kinases, are a rapidly expanding family of genes thought to play an important role in the development and oncogenesis of various tissues. However, very little experimental evidence supports this hypothesis. Using RNA fingerprinting, we detected increased expression of Lerk-5 mRNA in human melanocytes as a response to the tumor-promoting drug 12-O-tetradecanoylphorbol-13-acetate, which suggests a possible role of the Lerks in melanoma tumorigenesis and progression. Therefore, we studied Lerk-5 mRNA expression in various melanoma cell lines and tissues of melanocytic tumors by semiquantitative reverse transcription-PCR. Modest expression of Lerk-5 mRNA was found in two melanoma cell lines derived from early primary tumors (WM35 and WM1645B); two metastatic cell lines tested showed a 3.9-fold increased transcript abundance when compared to the primary cell lines (RPMI-7951 and SK-Mel5). Progeny of a melanoma cell line with very low Lerk-5 mRNA abundance (WM35) showed a 5-fold increase in Lerk-5 mRNA expression when it was selected for higher tumorigenicity and multicytokine resistance by passaging in nude mice or repeated high-dose UVB irradiation. Consistent with these experimental data, we found high levels of Lerk-5 mRNA expression in advanced primary malignant melanomas and metastases (n = 22) but significantly lower or undetectable mRNA expression in benign melanocytic nevi (n = 9; P < 0.001). We conclude that increased Lerk-5 expression possibly reflects or induces an increased potential of growth, tumorigenicity, and metastatic abilities in human melanomas. This makes the yet to be elucidated eph-related receptor tyrosine kinase/Lerk signaling system a potential new source for molecular markers as well as a target for new therapies.
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HISTORY AND ADMISSION FINDINGS: Six weeks before admission of a 47-year-old man with known rectal carcinoma, small nodular metastases had occurred over the front of both his thighs. Examination showed many aggregatet cuti-color or livid nodes, diameter 0.5 cm. The patient's poor general condition excluded the usual palliative measures. TREATMENT AND COURSE: Photochemotherapy of the skin metastases with indocyanine green (ICG; absorption maximum 805 nm), a non-toxic dye approved for diagnostic purposes, was undertaken on a trial basis. The dye, being bound to plasma proteins, is retained in the intravacular space. Immediately after administration of the dye (2.5 mg/kg intravenously) the skin metastases were irradiated by diode laser (lambda = 805 nm, 100 J/cm2, 3 W/cm2, radiation diameter 2 cm). This necrosed the metastases and clinically as well as histologically resulted in their complete disappearance with scarring of the treated area. CONCLUSION: This case illustrates the effectiveness of photochemotherapy with ICG against solid skin tumours of increased microvascular density.
In mammalian cells, UV induces a limited set of early transcribed genes, which overlaps with the set of genes induced by tumor promoting drugs such as 12-O-tetradecanoyl phorbol-13-acetate (TPA). Among these are genes for transcription factors, the activation of which leads to complex secondary changes in expression of multiple target genes. How these delayed pleiotropic UV effects on transcription may contribute to initiation of melanoma skin cancer is poorly understood. We analyzed changes in the relative abundances of 1900 transcripts in newborn human melanocytes 8 h after treatment with UVB, TPA, and cycloheximide in all combinations, using RNA arbitrarily primed PCR for differential display. The relative abundances of 205 transcripts (11% of all transcripts surveyed) were altered by one or more of the treatment combinations. Fourteen of the 77 genes up-regulated by TPA were also up-regulated by UVB, but 60 of the TPA up-regulated genes were down-regulated by UVB, indicating both intersecting and independent signal transduction pathways for UVB and TPA. A number of UVB and TPA target genes were identified by cDNA cloning. Consistent with UVB induction of a partly transformed phenotype in mammalian cells, UVB antagonized the TPA-inducible expression of tumor-suppressive tropomyosin 3 mRNA. In addition, UVB may impair mitochondrial functioning and induce oxidative stress by strong down-regulation of mitochondrial transcription. Finally, increased expression of the dihydropteridine reductase gene, a major regulator of the cellular tetrahydrobiopterin pool, was linked to the UV pathway.
BACKGROUND AND OBJECTIVE: Er:YAG lasers are known to superficially ablate skin and other tissues with minimal thermal coagulation zones. The ablation efficacy and thus the clinical applicability of these lasers, however, was limited due to small beam diameters and repetition rates. Aim of this study was to determine the ablation efficacy and the amount of thermal damage with a new high-power high-repetition-rate Er:YAG laser and to find optimal treatment parameters for skin ablation. STUDY DESIGN/MATERIALS AND METHODS: In vitro and some in vivo ablation trials on human skin were performed with the Er:YAG laser (MCL 29, Aesculap-Meditec, Heroldsberg, Germany, 2.94 microns, max. 500 mJ per pulse, 250 microseconds pulse length, 3 or 4 mm spot size, repetition rate 7-10 Hz) and evaluated microscopically. RESULTS: The ablation threshold was around 1.6 J/cm2. The ablation rates increased linearly with the fluence, and the above-threshold ablation efficacy was around 2.5 microns per pulse per J/cm2, leading to ablation velocities of 70-100 microns per second and higher. With increasing pulse numbers applied to one tissue spot, the ablation per pulse decreased significantly. The amount of thermal damage was clearly dependent on the number of pulses applied (around 25 microns with < 10 imp., up to 100 microns with 40 imp.), whereas higher fluences increased the coagulation zones only minimally. The in vivo trials confirmed these results: overlapping pulses in the 4 J/cm2-range, applied in a sweeping motion, proved optimal for an efficient skin ablation with a smooth resulting surface and a thermal damage zone not exceeding 50 microns. CONCLUSIONS: The high power and the high repetition frequency make this laser a fast and effective tool for skin ablation without increasing the thermal damage, but the ablation remains limited to the superficial dermis, since hemostasis cannot be achieved due to the absence of coagulation.
In recent years there has been increased interest in diseases showing degeneration of dermal elastic tissue. Mid dermal elastolysis is a rare dermatosis, which is histopathologically characterized by mid dermal loss of elastic tissue. Both papular and patchy forms, as well as inflammatory and non-inflammatory variants, have been described. A 70-year-old woman had annular patches. In their center the clinical and histopathological findings suggested non-inflammatory mid dermal elastolysis whereas the red and slightly elevated margins showed clinical and histopathological features of annular elastolytic giant cell granuloma. Based on our case and a review of the literature, we discuss the differential diagnosis of dermal elastolysis and hypothesize that a number of lesions histologically showing mid dermal elastolysis may represent different inflammatory or non-inflammatory stages of one disease which may overlap or change from one form into another.