Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.     

Inhibitors of bacterial N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) and demonstration of in vitro antimicrobial activity

The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor l-captopril (IC₅₀ = 3.3 μM, K_i = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli.     

On the history of <Emphasis Type="Italic">Brasenia</Emphasis> Schreb. in the European Pleistocene

Brasenia Schreb. is a monotypic genus in the Cabombaceae, present nowadays on all continents except Europe and Antarctica. This thermophilous aquatic plant, which originated in the Tertiary, was a frequent element of aquatic plant life during the interglacial stages of the European Pleistocene. A systematic review of the palaeobotanical records of Brasenia pollen and seeds reveals its history in Europe from the Plio-Peistocene until the Eemian interglacial. Remains of Brasenia were typical for the climatic optima during each of these stages of the Pleistocene. In this paper the diversity of fossil Brasenia species is also shown. The most abundant and morphologically diverse seeds were found in sediments from eastern European sites. Brasenia species became extinct in Europe at the end of the last interglacial or at the beginning of the Weichselian glaciation. Different scenarios for their disappearance are proposed, including the specificity of the floral cycle, probable poor dispersal of seeds, or the scarcity of suitable water bodies for it to survive.     

Soluble intercellular adhesion molecule-1 (sICAM-1): an overview

Soluble intercellular adhesion molecule-1 (sICAM-1) represents a circulating form of ICAM-1 that is constitutively expressed or is inducible on the cell surface of different cell lines. It serves as a counter-receptor for the lymphocyte function-associated antigen (LFA-1). Interaction between ICAM-1, present on endothelial cells, and LFA-1 facilitates leukocyte adhesion and migration across the endothelium. ICAM-1 and its circulating form have been implicated in the development of any number of diseases.     

Quantitative immunogold study of increased expression of metallothionein-I/II in the brain perivascular areas of diabetic scrapie-infected mice

Quantitative immunogold procedure was used to study the distribution of metallothionein I/II (MT-I/II) at the ultrastructural level in the perivascular areas, including microvascular endothelial cells (ECs) and astrocytes with their perivascular end-feet, in brains of scrapie-infected hyperglycemic (diabetic) and normoglycemic (non-diabetic) mice. Samples of the fronto-parietal cortex obtained from diabetic and non-diabetic scrapie-infected, as well as from non-infected (control) SJL/J mice, were processed for immunocytochemical examination. In control mice, the labelling of the ECs was of low intensity, restricted to few immunogold particles in the cytoplasm. More intense labelling was present in the cytoplasm of astrocytic perivascular processes and perikarya, where it was associated with endoplasmic reticulum and fibrils. A few immunosignals were also present inside the nuclei of astrocytes. In diabetic mice the labelling of the EC cytoplasm was slightly increased, whereas in the cytoplasm of perivascular processes and pericarya of astrocytes, including their nuclei, there was significant enhancement of labelling. In these cells the density of immunosignals was highest in the areas of cytoplasm containing bundles of fibrils. In non-diabetic, scrapie-infected mice the intensity of immunolabelling was higher than in control mice but slightly lower than in diabetic mice. These results are similar to those in Alzheimer’s disease reported by other authors, and suggest that neurodegenerative diseases as well as metabolic stress enhance the metallothionein expression in perivascular regions of brain cerebral cortex, predominantly in astrocytes.     

Inotropic drugs in treatment of heart failure--advantages and adverse reactions]

Mechanism of action, hemodynamic effects, efficacy of both shortterm and chronic administration of available inotropic drugs are discussed. An emphasis is on the possible mechanism of detrimental sequelae of the chronic inotropic stimulation of the failing heart.     

Hyperspectral and Thermal Imaging of Oilseed Rape (Brassica napus) Response to Fungal Species of the Genus Alternaria

In this paper, thermal (8-13 µm) and hyperspectral imaging in visible and near infrared (VNIR) and short wavelength infrared (SWIR) ranges were used to elaborate a method of early detection of biotic stresses caused by fungal species belonging to the genus Alternaria that were host (Alternaria alternata, Alternaria brassicae, and Alternaria brassicicola) and non-host (Alternaria dauci) pathogens to oilseed rape (Brassica napus L.). The measurements of disease severity for chosen dates after inoculation were compared to temperature distributions on infected leaves and to averaged reflectance characteristics. Statistical analysis revealed that leaf temperature distributions on particular days after inoculation and respective spectral characteristics, especially in the SWIR range (1000-2500 nm), significantly differed for the leaves inoculated with A. dauci from the other species of Alternaria as well as from leaves of non-treated plants. The significant differences in leaf temperature of the studied Alternaria species were observed in various stages of infection development. The classification experiments were performed on the hyperspectral data of the leaf surfaces to distinguish days after inoculation and Alternaria species. The second-derivative transformation of the spectral data together with back-propagation neural networks (BNNs) appeared to be the best combination for classification of days after inoculation (prediction accuracy 90.5%) and Alternaria species (prediction accuracy 80.5%).     

Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation

Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels.     

Purification and characterization of cytoplasmic 14C-arginine rich basic proteins of Ehrlich ascites tumor cells

Summary Arginine rich basic proteins from cytoplasm of Ehrlich ascites tumor cells have been separated and partially characterized. All proteins show a cationic character with the following isoelectric points: 8.45, 8.60, 8.70, 8.90, and possess various amount of arginine. The protein of the highest molecular weight (75000) has the greatest amount of arginine (18.1%), specific radioactivity (19760 cpm/mg, min) and isoelectric point (8.9). The significance of those proteins in the cytoplasm of tumor cells has been discussed briefly.     

Detection of substance P and its mRNA in human blast cells in childhood lymphoblastic leukaemia using immunocytochemistry and in situ hybridisation

The study focused on determining the expression of substance P (SP) in neoplastic cells of childhood acute lymphoblastic leukaemia (ALL) at the levels of its mRNA and the protein production. The study group comprised 44 children treated for ALL in the Department of Paediatric Haematology and Oncology, Karol Marcinkowski University of Medical Sciences in Poznań, in the years 1999-2001. Bone marrow smears were obtained by needle biopsy. Expression of SP was examined by immunocytochemistry with specific antibody against human SP and by in situ hybridisation with anti-mRNA 5'-biotinylated probe. The results of the study demonstrated that SP could be detected in the cytoplasm of lymphoblasts (mean percentage of 81.8% for immunocytochemical and 84.5% for in situ hybridisation technique) in leukaemias of the common and T-cell types. SP was absent from blasts in B-cell leukaemia and from normal haematopoietic, cells in children of the control group. The results show that lymphoblasts of common and T-cell origin acquire the capability to synthesise SP after their neoplastic transformation in childhood acute leukaemia. SP may be involved in auto- and paracrine mechanisms capable of inducing hyperplasia of the neoplastic cells.