34 research outputs found

    Synthesis, antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives

    Get PDF
    Two series of benzimidazole derivatives were sythesised. The first one was based on 5,6-dinitrobenzimidazole, the second one comprises 2-thioalkyl- and thioaryl-substituted modified benzimidazoles. Antibacterial and antiprotozoal. activity of the newly obtained compounds was studied. Some thioalkyl derivatives showed remarkable activity against nosocomial strains of Stenotrophomonas malthophilia, and an activity comparable to that of metronidazole against Gram-positive and Gram-negative bacteria. Of the tested compounds, 5,6-dichloro-2-(4-nitrobenzylthio)-benzimidazole showed the most distinct antiprotozoal activity

    Percutaneous lung needle biopsies : utility and complications in various chest lesions : a single-institution experience

    Get PDF
    Purpose: It is crucial to obtain a specific diagnosis before treatment of chest pathology is initiated. The purpose of the study is to present the utility of percutaneous biopsies, core and fine-needle aspiration, in various thoracic lesions, and related complications. Material and methods: A total of 593 transthoracic biopsies were performed in the Department of Radiology between 2013 and 2016. Fine-needle aspiration biopsy (FNAB) and core biopsy (CB) were implemented. The procedures were divided into four groups according to the location of the pathology: lung lesions (LL - 540), mediastinal masses (MM - 25), chest wall tumours (CWT - 13), and pleural lesions (PL - 15). The lung lesion group was divided into two subgroups: lung nodules and lung infiltrations. All groups were analysed in respect of diagnostic accuracy, pathological findings, and complication rate. Results: Pathological diagnosis was confirmed in 447 cases after all 593 procedures. The sensitivity of malignancy diagnosis in the group of lung tumours was 75% for FNAB and 89% for CB. The sensitivity in other groups, where CB was a preferable technique, was counted for lung infiltration, mediastinal masses, chest wall tumours, and pleural lesions and amounted to 83.3%, 90.9%, 100%, and 85.7%, respectively. In the group of lung tumours malignancy was confirmed most commonly (79%), while in the lung infiltration group benign processes dominated (83%). There was no statistical difference between the pneumothorax rate after CB and FNAB. Haemoptysis appeared more often after CB. Conclusions: FNAB and CB are useful, safe, and sensitive tools in the diagnostic work-up. They can both be used to diagnose almost all chest pathologies

    Combining low-dose CT-based radiomics and metabolomics for early lung cancer screening support

    Full text link
    Due to its predominantly asymptomatic or mildly symptomatic progression, lung cancer is often diagnosed in advanced stages, resulting in poorer survival rates for patients. As with other cancers, early detection significantly improves the chances of successful treatment. Early diagnosis can be facilitated through screening programs designed to detect lung tissue tumors when they are still small, typically around 3mm in size. However, the analysis of extensive screening program data is hampered by limited access to medical experts. In this study, we developed a procedure for identifying potential malignant neoplastic lesions within lung parenchyma. The system leverages machine learning (ML) techniques applied to two types of measurements: low-dose Computed Tomography-based radiomics and metabolomics. Using data from two Polish screening programs, two ML algorithms were tested, along with various integration methods, to create a final model that combines both modalities to support lung cancer screening

    Glutamate, GABA and Acetylcholine Signaling Components in the Lamina of the Drosophila Visual System

    Get PDF
    Synaptic connections of neurons in the Drosophila lamina, the most peripheral synaptic region of the visual system, have been comprehensively described. Although the lamina has been used extensively as a model for the development and plasticity of synaptic connections, the neurotransmitters in these circuits are still poorly known. Thus, to unravel possible neurotransmitter circuits in the lamina of Drosophila we combined Gal4 driven green fluorescent protein in specific lamina neurons with antisera to γ-aminobutyric acid (GABA), glutamic acid decarboxylase, a GABAB type of receptor, L-glutamate, a vesicular glutamate transporter (vGluT), ionotropic and metabotropic glutamate receptors, choline acetyltransferase and a vesicular acetylcholine transporter. We suggest that acetylcholine may be used as a neurotransmitter in both L4 monopolar neurons and a previously unreported type of wide-field tangential neuron (Cha-Tan). GABA is the likely transmitter of centrifugal neurons C2 and C3 and GABAB receptor immunoreactivity is seen on these neurons as well as the Cha-Tan neurons. Based on an rdl-Gal4 line, the ionotropic GABAA receptor subunit RDL may be expressed by L4 neurons and a type of tangential neuron (rdl-Tan). Strong vGluT immunoreactivity was detected in α-processes of amacrine neurons and possibly in the large monopolar neurons L1 and L2. These neurons also express glutamate-like immunoreactivity. However, antisera to ionotropic and metabotropic glutamate receptors did not produce distinct immunosignals in the lamina. In summary, this paper describes novel features of two distinct types of tangential neurons in the Drosophila lamina and assigns putative neurotransmitters and some receptors to a few identified neuron types

    Variants of the 5′-terminal region of p53 mRNA influence the ribosomal scanning and translation efficiency

    No full text
    Abstract The p53 protein is one of the major cell cycle regulators. The protein is expressed as at least twelve protein isoforms resulting from the use of alternative promoters, alternative splicing or downstream initiation codons. Importantly, there is growing evidence that translation initiation of p53 mRNA may be regulated by the structure and length of the naturally occurring variants of the 5′-terminal region of p53 mRNA transcripts. Here, several mRNA constructs were synthesized with variable length of the p53 5′-terminal regions and encoding luciferase reporter protein, and their translation was monitored continuously in situ in a rabbit reticulocyte lysate system. Moreover, four additional mRNA constructs were prepared. In two constructs, the structural context of AUG1 initiation codon was altered while in the other two constructs, characteristic hairpin motifs present in the p53 5′-terminal region were changed. Translation of the last two constructs was also performed in the presence of the cap analogue to test the function of the 5′-terminal region in cap-independent translation initiation. Superposition of several structural factors connected with the length of the 5′-terminal region, stable elements of the secondary structure, structural environment of the initiation codon and IRES elements greatly influenced the ribosomal scanning and translation efficiency

    Modulation of p53 Expression Using Antisense Oligonucleotides Complementary to the 5′-Terminal Region of p53 mRNA In Vitro and in the Living Cells

    Get PDF
    <div><p>The p53 protein is a key player in cell response to stress events and cancer prevention. However, up-regulation of p53 that occurs during radiotherapy of some tumours results in radio-resistance of targeted cells. Recently, antisense oligonucleotides have been used to reduce the p53 level in tumour cells which facilitates their radiation-induced apoptosis. Here we describe the rational design of antisense oligomers directed against the 5′-terminal region of p53 mRNA aimed to inhibit the synthesis of p53 protein and its ΔNp53 isoform. A comprehensive analysis of the sites accessible to oligomer hybridization in this mRNA region was performed. Subsequently, translation efficiency from the initiation codons for both proteins in the presence of selected oligomers was determined in rabbit reticulocyte lysate and in MCF-7 cells. The antisense oligomers with 2′-<i>O</i>Me and LNA modifications were used to study the mechanism of their impact on translation. It turned out that the remaining RNase H activity of the lysate contributed to modulation of protein synthesis efficiency which was observed in the presence of antisense oligomers. A possibility of changing the ratio of the newly synthetized p53 and ΔNp53 in a controlled manner was revealed which is potentially very attractive considering the relationship between the functioning of these two proteins. Selected antisense oligonucleotides which were designed based on accessibility mapping of the 5′-terminal region of p53 mRNA were able to significantly reduce the level of p53 protein in MCF-7 cells. One of these oligomers might be used in the future as a support treatment in anticancer therapy.</p></div

    The Role of Structural Elements of the 5'-Terminal Region of p53 mRNA in Translation under Stress Conditions Assayed by the Antisense Oligonucleotide Approach.

    No full text
    The p53 protein is one of the major factors responsible for cell cycle regulation and stress response. In the 5'-terminal region of p53 mRNA, an IRES element has been found which takes part in the translational regulation of p53 expression. Two characteristic hairpin motifs are present in this mRNA region: G56-C169, with the first AUG codon, and U180-A218, which interacts with the Hdm2 protein (human homolog of mouse double minute 2 protein). 2'-OMe modified antisense oligomers hybridizing to the 5'-terminal region of p53 mRNA were applied to assess the role of these structural elements in translation initiation under conditions of cellular stress. Structural changes in the RNA target occurring upon oligomers' binding were monitored by the Pb2+-induced cleavage method. The impact of antisense oligomers on the synthesis of two proteins, the full-length p53 and its isoform Δ40p53, was analysed in HT-29, MCF-7 and HepG2 cells, under normal conditions and under stress, as well as in vitro conditions. The results revealed that the hairpin U180-A218 and adjacent single-stranded region A219-A228 were predominantly responsible for high efficacy of IRES-mediated translation in the presence of stress factors. These motifs play a role of cis-acting elements which are able to modulate IRES activity, likely via interactions with protein factors

    Modified antisense oligomers.

    No full text
    <p>In oligomer sequences: italic letters –2′-<i>O</i>-methyl monomers, N<sub>L</sub> – LNA, N<sub>s</sub> – phosphorothioates; (+) denotes antisense oligonucleotides complementary to <i>Firefly</i> luciferase coding sequence.</p
    corecore