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Martin, Slovakia

Kohler R.,Institute of Medical Biology
Pflugers Archiv European Journal of Physiology | Year: 2010

In the cardiovascular system, Ca2+-activated K +-channels (KCa) are considered crucial mediators in the control of vascular tone and blood pressure by modulating the membrane potential and shaping Ca2+-dependent contraction. Vascular smooth muscle cells express the BKCa channel which fine-tunes contractility by providing a negative feedback on Ca2+-elevations. BKCa channel's ionconducting β-subunit is encoded by the KCa1.1 gene, and the accessory and Ca2+-sensitivity modulating β1-subunit is encoded by the KCNMB1 gene. Vascular endothelial cells express the calmodulin-gated KCa channels IKCa (encoded by the KCa3.1 gene) and SKCa (encoded by the KCa2.3 gene). These two channels mediate endothelial hyperpolarization and initiate the endothelium-derived hyperpolarizing factor-dilator response. Considering these essential roles of KCa in arterial function, mutations in KCa genes have been suspected to contribute to cardiovascular disease in humans. So far, DNA sequence analysis in the population and patient cohorts has identified single-nucleotide polymorphisms (SNPs) in the BKCa β1-subunit gene as well as in the α-subunit gene (KCa1.1). Some of these SNPs produce amino acid exchanges and evoke alterations of channel functions ("gain-of-function" as well as "loss-offunction"). Moreover, the epidemiological studies showed that the presence of the E65K polymorphism in, e.g., BKCa β1-subunit gene (producing a "gain-of-function") lowers the prevalence for severe hypertension and myocardial infarction. Other SNPs in the BKCa α-subunit gene and also in the KCa3.1 gene expressed in the endothelium have been suggested to increase the risk of cardiovascular disease. These findings from sequence analysis of human KCa genes, and epidemiological studies thus provide evidence that genetic variations and mutations in KCa channel genes contribute to human cardiovascular disease. © Springer-Verlag 2009. Source


Hjelmevoll S.O.,University Hospital of North Norway | Olsen M.E.,University Hospital of North Norway | Sollid J.U.E.,Institute of Medical Biology | Haaheim H.,University Hospital of North Norway | And 5 more authors.
Acta Dermato-Venereologica | Year: 2012

Culture is commonly regarded as the gold standard for diagnosis of Neisseria gonorrhoeae. However, nucleic acid amplification tests (NAATs) have rapidly replaced culture for diagnostics in many settings. The aim of the present study was to investigate the appropriate time for test-of-cure (TOC) when NAATs are used for diagnosis of gonorrhoea. In total, 30 patients (28 men and 2 women) provided urethral, cervical, rectal or pharyngeal specimens for TOC. All included patients, except one who did not return for second TOC before day 19, tested negative within 2 weeks after treatment with cefixime 400 mg × 1. Antimicrobial susceptibility testing showed that 68% of the culture-positive strains were resistant to ciprofloxacin. Thus, the recommended empirical treatment with ciprofloxacin in Norway should be changed immediately. TOC can be performed 2 weeks after treatment when NAATs are used for diagnosis of gonorrhoea. © 2012 The Authors. Source


Bartos V.,Faculty Hospital in Zilina | Adamicova K.,Institute of Pathological Anatomy | Kullova M.,Faculty Hospital in Zilina | Pec M.,Institute of Medical Biology
Klinicka Onkologie | Year: 2012

Background: Basal cell carcinoma (BCC) recurrences are relatively frequent event in a routine dermatologic practice. One of the most important factor which impacts risk of their development is a histomorphological appearance of tumor. Design: The purpose of our study was to compare histological types of primary and corresponding relapsing BCCs of the skin. Material and methods: The study included 36 cases of BCC recurrences from 34 patients, 17 women and 17 men. The patients ranged in age from 32 to 97 years, with a mean age of 67.1 years at the time of (the first) recurrence. Results: Both tumor groups generally exhibited the same proportion of indolent and aggressive histological phenotype. In 21 cases (58.4%), we found an identical histological BCC type in primary and subsequent relapsing lesion. In 3 cases (8.3%), primary lesion showed indolent histological features without aggressive-growth component, while recurrent tumor already manifested it. Conversely, in next 3 cases (8.3%) primary tumor exhibited focal infiltrative-growth features and corresponding relapsing lesion did not. Of the remainig 9 cases (25%), histomorpological phenotype was not identical, but it showed the same prognostic histological tumor variant. Conclusion: Based on the results of our study it can be assumed that a BCC recurrence is a dynamic histogenetic process, during which the phenotypic transformation and the changes in histomorphological picture of lesions occur, probably as a result of the interactions between cancer cells and re-modulated surrounding stroma. Source


Stewart C.L.,Institute of Medical Biology
Nucleus (Austin, Tex.) | Year: 2014

Pairing of homologous chromosome is a unique event in meiosis that is essential for both haploidization of the genome and genetic recombination. Rapid chromosome movements during meiotic prophase are a key feature of the pairing process. This is usually telomere-led, and in metazoans is dependent upon microtubules and dynein. Chromosome movements culminate in the formation of a meiotic "bouquet" in which nuclear envelope-associated telomeres are clustered at the centrosomal pole of the nucleus. Bouquet formation is thought to facilitate homolog pairing. Recent studies reveal that coupling of telomeres to cytoplasmic dynein is mediated by SUN1 in the inner nuclear membrane (INM) and KASH5 a novel protein of the outer nuclear membrane (ONM). Together SUN1 and KASH5 assemble to form a transluminal LINC (linker of the nucleoskeleton and cytoskeleton) complex that spans both nuclear membranes. SUN1 forms attachment sites for telomeres at the INM while KASH5 functions as a dynein adaptor at the ONM. In mice deficient in KASH5, homologous chromosome pairing does not occur. The result is that meiosis is arrested at the leptotene/zygotene stage of meiotic prophase 1, and as a consequence both male and female mice are infertile. This study demonstrates an essential role for dynein directed telomere movement during meiotic prophase. Source


Ovarian cancer kills more than 150,000 women globally each year, but the molecular and cellular events behind it remain unclear. "We need to understand the normal cell biology of the ovary before we can begin to understand what goes wrong during cancer, for example," says Nick Barker of the A*STAR team. At the A*STAR Institute of Medical Biology, Barker and his team studied the regeneration and repair of the surface cell layer—the epithelium—of the ovary and fallopian tube, along with collaborators at the National University of Singapore. During ovulation this crucial layer of cells undergoes repeated cycles of tearing and subsequent repair (see image). Little is known, however, about the molecular mechanism of the tissue renewal process, or how it is disrupted during disease. Resident stem cells drive such tissue maintenance activities in many epithelial layers throughout the body, explains Barker, but similar stem cells have never been proven to exist in the ovary. Previous work by Barker and his colleagues had shown that a cell-surface receptor protein, known as Lgr5, acts as a marker identifying stem cells in various epithelial layers, including those of the intestine, stomach and kidney. The most recent work has identified the protein on cells of the ovaries and fallopian tubes of mice which confirms the presence and activity of resident stem cells that can maintain the ovarian epithelium. "This will give scientists the ability to decipher the biology of these stem cells in normal healthy tissue," comments Barker. He explains that mutations in stem cells are likely to be a major cause of cancers of the ovarian epithelium. This is highly probable, he says, given that the Lgr5-bearing stem cells identified by his previous work are a major source of epithelial cancers of the stomach and intestine. Next Barker and his team plan to create targeted mutations in specific genes and analyze the possible role of these mutations in ovarian cancer. They also hope to build on the work with mice by purifying and growing human ovarian stem cells and epithelia in culture, providing insights that will be directly relevant to medical applications. "This basic research is a prerequisite for eventually being able to develop more targeted and more effective therapies to treat ovarian disease," says Barker. Explore further: Attacking bowel cancer on two fronts More information: Annie Ng et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia, Nature Cell Biology (2014). DOI: 10.1038/ncb3000

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