[Renal cell carcinoma diagnosis and prognosis within the context of the WHO classification 2016]. / Histopathologische Diagnose und Prognose des Nierenzellkarzinoms im Kontext der WHO-Klassifikation 2016.

BACKGROUND: Histological classification of renal cell carcinoma (RCC) has become more and more important for clinical management, but relatively few is known regarding the swiftness with which the 2016 World Health Organization (WHO) classification of RCC was adopted in the daily routine diagnostics. AIM: To retrospectively review the histological diagnosis of RCC within the context of 2016 WHO classification followed by survival analysis. MATERIAL AND METHODS: Retrospective register based analysis of RCC diagnosis between 1998 and 2017 and survival analysis. RESULTS: 1440 RCC cases were registered between 1998 and 1917. According to 2016 WHO classification, 77.7% clear cell RCC and 22.3% non-clear cell RCC were diagnosed. A total of 37 rare subtypes were recorded, among those 1% MiT family translocation RCC, 0.35% acquired cystic disease-associated RCC, 0.35% multilocular cystic renal neoplasm of low malignant potential, 0.35% collecting duct carcinoma, 0.3% mucinous tubular and spindle cell carcinoma, 0.1% clear cell papillary RCC and 0.1% RCC with (angio)leiomyomatous stroma. Cox regression analysis showed significant different overall survival and progression-free survival between the histological subtypes. DISCUSSION: The complexity of the 2016 WHO classification of RCC put high demands on histopathological diagnostics. At University Medicine Center Rostock morphological distinct RCC entities have been mostly diagnosed by conventional means via hematoxillin and eosin stained slides, but beyond immunohistochemistry additionally molecular techniques were established. The histologic subtyping of RCC according to 2016 WHO classification has prognostic significance and might have predictive significance for unique therapeutic approaches.

[Autoimmune-Mediated Encephalomyelitis: a Heterogeneous Entity in Between Neurology and Psychiatry]. / Autoimmunvermittelte Enzephalomyelitiden: Eine heterogene Krankheitsgruppe zwischen Psychiatrie und Neurologie.

Within the last decade, autoantibody-associated encephalitis and encephalomyelitis have stepped into the focus of clinical research and practice. Besides the "classic" autoantibodies against intracellular neuronal antigenes, a growing number of antibodies directed against pre- and postsynaptic surface proteins of neurons have been described since the millennium change. Whereas the "classic" are closely linked to paraneoplastic syndromes, this association is loose for most of the yet known surface antigen-antibodies. The immune-mediated encephalomyelitic syndromes are thus classified not only by their clinical symptoms, but also by their specific antibodies. The definition of the entity of N-methyl-D-aspartate-receptor encephalitis is a prominent example. The presented work gives an overview on the clinical and pathological correlates and the underlying immunologic processes of autoantibody-associated encephalitis from a neuropsychiatric perspective.

[Diagnostic Workup and Treatment of Antibody-Related Encephalomyelitis]. / Diagnostik und Therapie von autoantikörpervermittelten Enzephalomyelitiden.

The results of laboratory tests for antineuronal antibodies in immune-mediated encephalitis nowadays are not only relevant for diagnostic purposes but are instead closely connected to outcome measures and treatment response. Besides the mere detection of antibodies, investigating the cerebrospinal fluid is indispensible to rule out an infectious etiology of encephalitis prior to the initiation of immunosuppressive treatment, whereas imaging studies are relevant to gain information on the temporal course of disease and for ruling out other etiologies, e. g. hippocampal gliomas. This work gives an overview on the clinical course and findings of laboratory, electroencephalography (EEG) and imaging studies in relevant types of autoimmune mediated encephalitis. Furthermore, it gives a synopsis on contemporary treatment strategies.

[The parameter "relative survival": Analysis of regional cancer registry data for prostate cancer]. / Der Parameter "Relatives Überleben" : Analyse regionaler Krebsregisterdaten beim Prostatakarzinom.

BACKGROUND: There is a lack of comparability of relative survival rates due to differences in regional mortality. OBJECTIVE: How should relative survival be calculated to be able to compare regional cancer mortality? MATERIALS AND METHODS: Calculation of relative survival rates of prostate cancer patients from a regional cancer registry using diagnosis year and stage, based on differential mortality tables. RESULTS: Calculation of relative survival for all prostate cancer patients shows a very slight excess mortality after 5 years compared to a matched general population. Introduction of new imaging techniques and PSA screening led to a change in the distribution of diagnosed stages. Differentiation by stage is therefore essential. Thus, patients with UICC stage I, II, and III have a very low excess mortality, while patients with a UICC stage IV have a significantly higher excess mortality; however, it is very surprising that the excess mortality of patients without specification of the UICC stage is similarly unfavorable as in the case of patients with UICC stage IV. CONCLUSION: If data from a regional cancer registry are used, adequate mortality tables from the catchment area of the registry should be used as a reference due to regional mortality differences. Thus, progress in patient survival can be more precisely mapped. With respect to prostate cancer patients, differential consideration by stage is also necessary because improved early detection methods has led to a change in the stage distribution and, thus, survival.

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52)--a novel type of 5-lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo.

BACKGROUND AND PURPOSE: 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH: We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS: HZ52, 1.5 mg·kg⁻¹ i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB(4) levels and protected mice (10 mg·kg⁻¹, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca²âº. CONCLUSIONS AND IMPLICATIONS: HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers.

Site-specific binding of the 9.5 kilodalton DNA-binding protein ORF80 visualized by atomic force microscopy.

Atomic force microscopy (AFM) has been used to examine the binding properties of the DNA-binding protein ORF80 to DNA. ORF80 is a 9.5 kDa protein that binds site-specifically to double-stranded DNA of the sequence TTAA-N(7)-TTAA. Direct sizing of the protein complexes on DNA fragments from the plasmid pRN1 with AFM shows that the protein ORF80 binds preferentially to two positions. These positions agree well with the ORF80 binding sites determined by footprinting analysis. The measurements allow an estimate of the stoichiometry of the DNA-protein complexes. In contrast to previous results, the single-molecule experiments suggest that only a low number of ORF80 molecules bind to a DNA-binding site.

Microscopic mechanisms of electric-field-induced alignment of block copolymer microdomains.

We investigate the microscopic mechanisms responsible for microdomain alignment in block copolymer solutions exposed to an electric field. Using time-resolved synchrotron small-angle x-ray scattering, we reveal two distinct processes, i.e., grain boundary migration and rotation of entire grains, as the two dominant microscopic mechanisms. The former dominates in weakly segregating systems, while the latter is predominant in strongly segregated systems. The kinetics of the processes are followed as a function of polymer concentration and temperature and are correlated to the solution viscosity.