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Biomedical subjects

Michael Landthaler

Publications and source records attributed to Michael Landthaler.

At least 37 records · Page 2Linked to original sources

Time-resolved investigations of singlet oxygen luminescence in water, in phosphatidylcholine, and in aqueous suspensions of phosphatidylcholine or HT29 cells.

Singlet oxygen was generated by energy transfer from the photoexcited sensitizer, Photofrin or 9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn), to molecular oxygen. Singlet oxygen was detected time-resolved by its luminescence at 1270 nm in an environment of increasing complexity, water (H2O), pure phosphatidylcholine, phosphatidylcholine in water (lipid suspensions), and aqueous suspensions of living cells. In the case of the lipid suspensions, the sensitizers accumulated in the lipids, whereas the localizations in the cells are the membranes containing phosphatidylcholine. By use of Photofrin, the measured luminescence decay times of singlet oxygen were 3.5 +/- 0.5 micros in water, 14 +/- 2 micros in lipid, 9 +/- 2 micros in aqueous suspensions of lipid droplets, and 10 +/- 3 micros in aqueous suspensions of human colonic cancer cells (HT29). The decay time in cell suspensions was much longer than in water and was comparable to the value in suspensions of phosphatidylcholine. That luminescence signal might be attributed to singlet oxygen decaying in the lipid areas of cellular membranes. The measured luminescence decay times of singlet oxygen excited by ATMPn in pure lipid and lipid suspensions were the same within the experimental error as for Photofrin. In contrast to experiments with Photofrin, the decay time in aqueous suspension of HT29 cells was 6 +/- 2 micros when using ATMPn.

Biophysics↗

Results of nonablative wrinkle reduction with a 1,450-nm diode laser: difficulties in the assessment of "subtle changes".

BACKGROUND AND OBJECTIVE: Nonablative resurfacing has proven its efficacy in vascular and pigmented lesions, while its capacity of substantial wrinkle reduction is still discussed controversially. We present the treatment results of a 1,450 nm diode laser for facial rhytides. METHODS: Thirty facial regions were treated with a 1,450 nm diode laser. Pre- and post treatment pictures were compared by the treating physician and two blinded observers. RESULTS: Even if mild improvement was rated in up to 35% of the post treatment pictures, a discrepancy shows up in the assessments of the three observers, presenting almost no congruency in the rating of improvement. CONCLUSIONS: Our study failed to provide convincing data on the efficacy of nonablative treatment of rhytides with the 1,450 nm diode laser. In this respect, we challenge objective judgment in the assessment of subtle changes in nonablative wrinkle reduction.

Adult↗

Overexpression and hyperphosphorylation of retinoblastoma protein in the progression of malignant melanoma.

Mutation, absence or abnormal functioning of retinoblastoma protein are fundamental elements of uncontrolled growth in human cancer. In this study, we analyze the expression of retinoblastoma protein and phosphorylated retinoblastoma protein in melanocytic tumors in vivo. Real-time RT-PCR and immunohistochemistry (tissue microarrays and conventional histological sections) reveal that retinoblastoma protein is progressively upregulated in advanced and metastatic malignant melanomas in vivo. However, this increase is paralleled by increased retinoblastoma protein inactivation due to protein phosphorylation. Interestingly, retinoblastoma protein phosphorylation occurs not homogeneously, but with a 'growth zone'-related pattern. In superficial spreading melanomas a subepidermal-lateral maximum of phosphorylated retinoblastoma protein can be frequently observed. Accordingly, nodular vertically invasive melanomas are characterized by a strong staining of phosphorylated retinoblastoma protein in deep-dermal invading protrusions of the tumor. Furthermore, Kaplan-Meier analysis of 13 cases of advanced melanomas with long-time follow-up suggests a significant negative impact of retinoblastoma protein phosphorylation on survival of melanoma patients independent of tumor thickness. We conclude that the evaluation of phosphorylated retinoblastoma protein in melanocytic tumors could become a helpful adjunct in clinicopathological routine.

Disease Progression↗

Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas.

In malignant melanomas, the loss of cell cycle control is thought to be due to a lack of retinoblastoma protein (pRb)-activity. Members of the previously described family of retinoblastoma-binding proteins (RBPs) are supposed to act as pRb-modulating factors. Based on RNA-fingerprinting of normal human melanocytes, we previously described a new family member with high sequence homology to the retinoblastoma-binding protein-2 (RBP-2), termed RBP2-Homolog 1 (RBP2-H1). Based on its UVB responsiveness, it was hypothesized that this gene may also play a role in melanocytic tumors. In the present study, we can confirm by real-time RT-PCR (six common melanocytic nevi, five advanced nodular melanomas and seven melanoma metastases) and immunohistochemistry (tissue microarrays: 52 melanocytic nevi, 60 melanomas, 60 metastases; and conventional sections: five common nevi, four advanced nodular melanomas, five melanoma metastases) that RBP2-H1 expression is progressively downregulated in advanced and metastatic melanomas in vivo with a certain intratumoral heterogeneity. Whereas benign melanocytic nevi are RBP2-H1 positive in about 70% of the cases, a lack of RBP2-H1 expression was found in 90% of the primary malignant melanomas and 70% of the melanoma metastases, respectively. Interestingly, a similar deficiency can be found in glioblastomas, but not epithelial cancers. In accordance to the in vivo data, established melanoma cell lines exhibit low but heterogeneous levels of RBP2-H1 expression. By co-immunoprecipitation, we provide the first evidence that a subfraction of total RBP2-H1 can bind to pRb, which makes this protein a true pRb-interacting factor. We conclude that loss of RBP2-H1 is a common finding in the progression of malignant melanomas. Since a direct interaction of RBP2-H1 and pRb seems possible, the loss of RBP2-H1 may possibly contribute to uncontrolled growth in malignant melanomas.

Base Sequence↗

Fibroadenoma of the axilla.

BACKGROUND: Ectopic, axillary breast tissue can develop any disease that affects the normal breast, including fibroadenoma. OBJECTIVE: To report and discuss a case of fibroadenoma of the axilla in a 23-year-old woman. METHODS: Case report and discussion of the rare entity of fibroadenoma of the axilla. RESULTS: The histology was identical to the fibroadenomas seen in the breast and those observed along the milk line. CONCLUSION: Differential diagnosis of an axillary tumor should include ectopic breast tissue.

Adult↗

The -2518 promotor polymorphism in the MCP-1 gene is associated with systemic sclerosis.

Factors influencing the initiation or progression of sclerosis in patients with systemic sclerosis (SSc) are poorly understood. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, which is upregulated in fibroblasts during development of sclerosis. In this study, we investigated the frequency of the functional -2518G MCP-1 promoter polymorphism in 18 patients with SSc and 139 healthy controls. In the lesional skin of the same SSc patients, expression of MCP-1 protein was examined by immunohistochemistry. To investigate a genotype/phenotype correlation, basal as well as tumor necrosis factor (TNF)-induced MCP-1 expression was analyzed in fibroblasts isolated from the skin of SSc patients with different MCP-1 genotypes by quantitative RT-PCR and ELISA. Genotyping for the -2518 (A/G) MCP-1 promotor polymorphism showed that GG homozygotes were significantly more frequent in patients with SSc than in controls (28%vs 6%). Results of immunohistochemistry revealed that MCP-1 was expressed in keratinocytes, infiltrating inflammatory cells, fibroblasts, and endothelial cells in scleroderma skin, whereas normal control skin showed no MCP-1 expression. MCP-1 expression in fibroblasts from GG-homozygote individuals tended to be stronger as compared to AG or AA genotypes. Furthermore, basal as well as TNF-induced MCP-1 expression of fibroblasts isolated from a GG-homozygote SSc patient was significantly higher than MCP-1 expression of fibroblasts isolated from heterozygote or AA-homozygote donors. The A -2518G polymorphism of the MCP-1 gene appears to affect MCP-1 expression of skin fibroblasts of patients with SSc. In accordance, the G/G genotype may predispose patients to SSc.

Adult↗

Gene expression profile changes between melanoma metastases and their daughter cell lines: implication for vaccination protocols.

Vaccination protocols based on autologous tumor material often require in vitro culturing of tumor cells to obtain enough cellular material for the production of the vaccine. Cancer cells and particularily melanoma cells are known for their genomic instability. Therefore, it can be assumed that melanoma cells acquire genomic changes and thereby changes in the transcriptome during in vitro culturing. This may lead to a shift of epitopes expressed on the tumor cells. We analyzed the transcriptome of in vitro cultured melanoma cells prepared from melanoma metastases. Comparing the gene expression changes between the tumors and their offspring cell lines, we demonstrate that with increasing passage numbers, gene expression changes increase drastically.

Cancer Vaccines↗

Selective photothermolysis of blood vessels following flashlamp-pumped pulsed dye laser irradiation: in vivo results and mathematical modelling are in agreement.

Laser therapy using the pulsed dye laser is the standard treatment for port-wine stains (PWS). But the mechanism of action has not been elucidated completely, yet. The dorsal skin-fold chamber model in hamsters was used to investigate the effects of laser treatment (lambda(em)=585 nm; pulse duration: 0.45 ms; fluence: 6 J per cm2) on blood vessels. Vessels (n=3394) were marked with FITC dextran (MW 150 kDa) and diameters (2-186 microm) were measured using intravital fluorescence microscopy up to 24 h following irradiation. Histology (H&E, TUNEL, CD31) was taken 1 or 24 h after irradiation. The experimental results were compared with the predictions of a mathematical model based on the finite-element method. Following irradiation treatment the number of unperfused vessels decreases with decreasing vessel diameter in vivo. Histology indicated a restriction of tissue injury to the irradiated area after 1 h. Blood vessels contained aggregated red blood cells. After 24 h tissue damage occurred also outside the irradiated area and thrombus formation was visible. These results were in agreement with the mathematical calculations. In addition to initial physical effects after pulsed dye laser treatment delayed biological processes contribute significantly to the reduction of perfused blood vessels. Because of incomplete photocoagulation of smaller blood vessels (diameter 2-16 microm) a complete bleaching of PWS seems to be unlikely.

Animals↗

Severe contact urticaria to guar gum included as gelling agent in a local anaesthetic.

We report the first case of a life-threatening immediate-type hypersensitivity caused by Dynexan, a local anaesthetic gel. After mucosal application by his dentist, a 63-year-old man rapidly developed urticaria, dyspnea and, at last, he collapsed and remained unconscious for 2 hr despite emergency care. While the standard prick tests were negative to all local anaesthetics tested including lidocaine, a 1-fold positive reaction was detected to Meyprogat 60, an ingredient of Dynexan. As the gelling agent Meyprogat represents a derivative of guar (synonymous guar gum, guaran, E-412), we subsequently tested different guar products derived from Cyamopsis tetragonoloba beans and, as control, the closely related locust bean gum E-410. In the prick-to-prick tests, the guar-derived food additive Provigel NAG 905 provoked a 1-fold positive reaction. Native guar beans pounded and resuspended in water showed a 2-fold positive reaction, whereas no reaction was found to derivatives of locust bean gum. Specific immunoglobulin E were negative in all cases. Despite the common use of guar as versatile food additive or gelling agent, this is the first case of a severe immediate-type hypersensitivity after mucosal contact.

Anaphylaxis↗

Comparison of two absorbable monofilament polydioxanone threads in intradermal buried sutures.

BACKGROUND AND OBJECTIVES: Two absorbable polydioxanone threads are compared regarding intraoperative handling qualities, scar dehiscence, and possible side effects. METHODS: In 30 excisions, half of each suture was performed with PDS II (Ethicon GmbH, Norderstedt, Germany), whereas the other half was closed with Serasynth (Serag-Wiessner, Naila, Germany). Clinical evaluation for scar spreading, spitting of the sutures, hypertrophic scarring, or suture granuloma was performed 3 and 6 months after surgery. RESULTS: No significant difference in scar spreading, hypertrophic scarring, or the incidence of suture granuloma was noted. A significantly lower frequency of spitting was seen with Serasynth than with PDS. The handling and suturing properties of SerasynthM were estimated to be slightly superior compared with those of PDS. CONCLUSION: Our study shows that PDS and Serasynth provide equal cosmetic results when applied in an appropriate suturing technique. Possibly owing to its better pliability, the frequency of spitting was lower with Serasynth.

Absorbable Implants↗

Congenital cartilaginous rests of the neck (wattles).

BACKGROUND: Congenital cartilaginous rests of the neck (wattles) are very rare, probably branchiogenic malformations. OBJECTIVE: To discuss the clinical and histologic features and the therapy of wattles. METHODS: We report a 4-year-old patient with symmetric exophytic nodules of the neck that had been present since birth. RESULTS: The two lesions, 0.5 3 0.5 cm, were removed. The histopathologic examination confirmed ectopic cartilaginous tissue. CONCLUSION: Wattles must be excised, including their cartilaginous core, after having sonographically excluded fistulae or sinuses.

Cartilage Diseases↗

Photodynamic therapy in dermatology--an update.

Topical photodynamic therapy (PDT) is a well-established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5-aminolevulinic acid (5-ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light-emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment.

Dermatology↗