Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma

Antimalarial activities of tetracycline (TC) and erythromycin (EM), alone or in combination with artemisinin (Qinghaosu, QHS), were studied using chloroquine (CQ)-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum in vitro. The antimalarial potency of TC (IC50 = 9862 nM for the CQ-sensitive parasite, 32414 nM for the CQ-resistant one) or EM (IC50 = 45787 nM for the CQ-sensitive parasite, 33397 nM for the CQ-resistant one) was much less than that of QHS (IC50 ranging from 25 to 40 nM). The CQ-resistant falciparum parasite displayed a cross-resistance to TC, while both the drug-sensitive and -resistant parasites exhibited similar responses to EM. However, antimalarial potency of EM appeared to be less than that of TC against the drug-sensitive parasite. When TC was combined with QHS, an additive interaction was observed against the CQ-sensitive falciparum parasite, while synergism was found with the CQ-resistant parasite. When EM was tested in combination with QHS, a potentiating interaction occurred with both the CQ-sensitive and resistant falciparum parasite. The above results indicated that the QHS combination with either TC or EM may be a promising antimalarial preparation with low recrudescence compared to artemisinin used alone in clinical practice.     

Interphase cytogenetics in pathology: principles, methods, and applications of fluorescence in situ hybridization (FISH)

Characteristic chromosome aberrations have been identified in various tumors. Fluorescence in situ hybridization (FISH) using specific probes that are generated by vector cloning or in vitro amplification and labeled with fluorescent dyes allow for the detection of these genetic changes in interphase cells. This technique, that is also referred to as "interphase cytogenetics", can be performed in cytological preparations as well as in sections of routinely formaldehyde-fixed and paraffin-embedded tissue. In cancer research and diagnostics, interphase cytogenetics by FISH is used to detect numerical chromosome changes and structural aberrations, e.g., translocations, deletions, or amplifications. In this technical overview, we explain the principles of the FISH method and provide protocols for FISH in cytological preparations and paraffin sections. Moreover, possible applications of FISH are discussed.     

Learning to Recognize Volcanoes on Venus

Dramatic improvements in sensor and image acquisition technology have created a demand for automated tools that can aid in the analysis of large image databases. We describe the development of JARtool, a trainable software system that learns to recognize volcanoes in a large data set of Venusian imagery. A machine learning approach is used because it is much easier for geologists to identify examples of volcanoes in the imagery than it is to specify domain knowledge as a set of pixel-level constraints. This approach can also provide portability to other domains without the need for explicit reprogramming; the user simply supplies the system with a new set of training examples. We show how the development of such a system requires a completely different set of skills than are required for applying machine learning to toy world domains. This paper discusses important aspects of the application process not commonly encountered in the toy world, including obtaining labeled training data, the difficulties of working with pixel data, and the automatic extraction of higher-level features.     

Interactive cytometry, chance or evil of bias?

Interactive selection of a limited number of cells in imaging cytometry for determining the DNA histogram of breast cancer cells as the best known prognosticator at the moment, implies statistical and systematic sampling problems. Analysis of histograms of 361 breast cancer aspirate specimens measured in two laboratories demonstrate the expected high statistical variations in view of the only 100 cells measured per case but also slight systematic differences. Controlled systematic sampling without pathological bias results in a somewhat higher malignancy grading than selective biased sampling. For this finding we have no explanation. The main result is, however, that we did not find the expected contrary which makes the argument for at least this application invalid that expert pathologists are needed for reliable interactive sampling.     

Selective and Brain‐Permeable Polo‐like Kinase‐2 (Plk‐2) Inhibitors That Reduce α‐Synuclein Phosphorylation in Rat Brain

Polo‐like kinase‐2 (Plk‐2) has been implicated as the dominant kinase involved in the phosphorylation of α‐synuclein in Lewy bodies, which are one of the hallmarks of Parkinson’s disease neuropathology. Potent, selective, brain‐penetrant inhibitors of Plk‐2 were obtained from a structure‐guided drug discovery approach driven by the first reported Plk‐2–inhibitor complexes. The best of these compounds showed excellent isoform and kinome‐wide selectivity, with physicochemical properties sufficient to interrogate the role of Plk‐2 inhibition in vivo. One such compound significantly decreased phosphorylation of α‐synuclein in rat brain upon oral administration and represents a useful probe for future studies of this therapeutic avenue toward the potential treatment of Parkinson’s disease.