[Current aspects in the prognosis of advanced melanoma]. / Aktuelle Aspekte in der Prognose des fortgeschrittenen Melanoms.

The therapy of metastatic melanoma has changed rapidly in recent years. Immune checkpoint blockade and targeted therapy have replaced less effective chemotherapies. New clinical studies also point towards a substantial benefit of these drugs for the adjuvant treatment of high-risk patients. Thus, the prognosis of advanced melanoma has improved. Nevertheless, it remains a life-threatening condition due to frequent relapses and progression of the disease. This article aims at providing an overview of current treatment strategies for metastasized melanoma and their impact on prognosis of the disease. In addition, changes in the recently published American Joint Committee of Cancer (AJCC) classification identifying groups at risk will be highlighted.

Facilitation dynamics of late somatosensory evoked potentials after sural nerve stimulation.

OBJECTIVE: Somatosensory evoked potentials (SSEPs) could be suitable for elucidating the properties of synaptic potentials (SPs). Two experiments were designed for this purpose. METHODS: 1st experiment: the sural nerve was stimulated in 13 subjects with single or trains of 3 stimuli (1Hz or 0.4Hz), the within train interstimulus interval (ISI) was stepwise extended from 2 to 10ms. Cz' against Fz, time interval 500ms. 2nd experiment: Gating was investigated in a paired stimulus paradigm with intervals of 0.7, 1, 2, 5s in 15 subjects after single and train stimuli (ISI 3ms) with equal stimulus and recording positions. RESULTS: 1st experiment: N1-P1, P1-N2a, and P2-N2b but not N37-P40 displayed a significant gain in amplitude following train stimuli compared with single stimuli. Significantly larger N1-P1 amplitude values were observed with 0.4Hz stimulus repetition compared with 1.0Hz. Short ISIs of 2-4ms led to higher N1-P1 amplitudes than obtained with longer ISIs of 7-10ms. 2nd experiment: recovery of the habituated N1-P1 amplitude was complete when the 2nd of 2 stimuli followed after 2s. CONCLUSIONS: SSEP vertex potential amplitudes (especially N1-P1) recorded after train stimuli presumably reflect the decay dynamics of excitatory postsynaptic potentials. Recovery of the habituated N1 (2nd experiment) was complete within 2s. SIGNIFICANCE: Our study may be relevant to study properties of excitatory synaptic potentials in diseases of the central nervous system such as e.g. epilepsy or migraine.

Epitope-specific monoclonal antibodies against human C-terminal procollagen alpha1(III)-propeptide.

We have generated monoclonal antibodies against recombinant C-terminal human procollagen alpha1(III) propeptide (PIIICP), produced in E. coli in high yields. The monoclonal antibodies were screened for epitope specificity using recombinant truncated PIIICP. Several antibodies were identified which recognized different regions of the PIIICP molecule. The ability of the antibodies to detect PIIICP antigens in human cell line lysates and supernatants was demonstrated. As PIIICP antigens are a key marker of extracellular matrix metabolism, the monoclonal antibodies described here should be of value for clinical and basic research.

Molecular systematics of the marine Dothideomycetes.

Phylogenetic analyses of four nuclear genes, namely the large and small subunits of the nuclear ribosomal RNA, transcription elongation factor 1-alpha and the second largest RNA polymerase II subunit, established that the ecological group of marine bitunicate ascomycetes has representatives in the orders Capnodiales, Hysteriales, Jahnulales, Mytilinidiales, Patellariales and Pleosporales. Most of the fungi sequenced were intertidal mangrove taxa and belong to members of 12 families in the Pleosporales: Aigialaceae, Didymellaceae,Leptosphaeriaceae, Lenthitheciaceae, Lophiostomataceae, Massarinaceae,Montagnulaceae, Morosphaeriaceae, Phaeosphaeriaceae, Pleosporaceae, Testudinaceae and Trematosphaeriaceae. Two new families are described: Aigialaceae and Morosphaeriaceae, and three new genera proposed: Halomassarina, Morosphaeria and Rimora. Few marine species are reported from the Dothideomycetidae (e.g. Mycosphaerellaceae, Capnodiales), a group poorly studied at the molecular level. New marine lineages include the Testudinaceae and Manglicolaguatemalensis in the Jahnulales. Significantly, most marine Dothideomycetes are intertidal tropical species with only a few from temperate regions on salt marsh plants (Spartina species and Juncus roemerianus), and rarely totally submerged (e.g. Halotthia posidoniae and Pontoporeia biturbinata on the seagrasses Posidonia oceanica and Cymodocea nodosum). Specific attention is given to the adaptation of the Dothideomycetes to the marine milieu, new lineages of marine fungi and their host specificity.

A class-wide phylogenetic assessment of Dothideomycetes.

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon.

Independent terrestrial origins of the Halosphaeriales (marine Ascomycota).

A phylogenetic study of marine ascomycetes was initiated to test and refine evolutionary hypotheses of marine-terrestrial transitions among ascomycetes. Taxon sampling focused on the Halosphaeriales, the largest order of marine ascomycetes. Approximately 1050 base pairs (bp) of the gene that codes for the nuclear small subunit (SSU) and 600 bp of the gene that codes for the nuclear large subunit (LSU) ribosomal RNAs (rDNA) were sequenced for 15 halosphaerialean taxa and integrated into a data set of homologous sequences from terrestrial ascomycetes. An initial set of phylogenetic analyses of the SSU rDNA from 38 taxa representing 15 major orders of the phylum Ascomycota confirmed a close phylogenetic relationship of the halosphaerialean species with several other orders of perithecial ascomycetes. A second set of analyses, which involved more intensive taxon sampling of perithecial ascomycetes, was performed using the SSU and LSU rDNA data in combined analyses. These second analyses included 15 halosphaerialean taxa, 26 terrestrial perithecial fungi from eight orders, and five outgroup taxa from the Pezizales. In these analyses the Halosphaeriales were polyphyletic and comprised two distinct lineages. One clade of Halosphaeriales comprised 12 taxa from 11 genera and was most closely related to terrestrial fungi of the Microascales. The second clade of halosphaerialean fungi comprised taxa from the genera Lulworthia and Lindra and was an isolated lineage among the perithecial fungi. Both the main clade of Halosphaeriales and the Lulworthia/Lindra clade are supported by the data as being independently derived from terrestrial ancestors.

Two assays for measuring fibrosis: reverse transcriptase-polymerase chain reaction of collagen alpha(1) (III) mRNA is an early predictor of subsequent collagen deposition while a novel serum N-terminal procollagen (III) propeptide assay reflects manifest fibrosis in carbon tetrachloride-treated rats.

Using a novel quantitative reverse transcriptase-polymerase chain reaction assay, we have determined the amount of specific mRNA for procollagen alpha(1) (III) (PIIIP) in the carbon tetrachloride (CCl(4)) model of liver fibrosis in rats. After a single week of CCl(4) application, the amount of PIIIP mRNA was increased approximately 10 times over the untreated control group and continued to increase to approximately 30 times after 7 weeks of intoxication. In this model substantial fibrosis was demonstrated by computer-aided morphometry after 5 to 7 weeks of treatment. Using recombinant murine N-terminal procollagen alpha(1) (III) propeptide (PIIINP), a novel sensitive immunoassay for the measurement of circulating PIIINP in rodent sera was established. An increase in PIIINP serum levels was observed after 5 to 7 weeks of CCl(4) intoxication. Our results suggest PIIIP gene expression is an early marker of tissue fibrosis. Early PIIIP gene expression is correlated with the extent of the subsequent fibrosis. PIIIP mRNA levels increase much earlier than conventional histological examination or PIIINP levels. PIIINP measurements with our new serum assay, on the other hand, are a good noninvasive marker of manifest fibrosis but are a poor marker of fibrogenesis.