Browsing by Author "Jenkins, R. O."
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Item Metadata only Accumulation of tropane alkaloids in hairy-root cultures of Datura stramonium(1991) Burbridge, A.; Gartland, K. M. A.; Jenkins, R. O.; Wolley, J. G.; Elliott, Malcolm C.Item Metadata only Adaptive changes in yeast membranes: catabolite repression and oxygen.(Portland Press, 1984) Jenkins, R. O.; Cartledge, T. G.; Lloyd, D.Item Metadata only Aerial release of bacteria from cot mattress materials and the sudden infant death syndrome.(Blackwell, 2005) Sherburn, R. E.; Jenkins, R. O.Item Open Access Albumin Is a Component of the Esterase Status of Human Blood Plasma(MDPI, 2023-06-20) Belinskaia, D. A.; Voronina, P. A.; Popova, P. I.; Voitenko, N. G.; Shmurak, V. I.; Vovk, M. A.; Baranova, T. I.; Batalova, A. A.; Korf, E. A.; Avdonin, P. V.; Jenkins, R. O.; Goncharov, N. V.The esterase status of blood plasma can claim to be one of the universal markers of various diseases; therefore, it deserves attention when searching for markers of the severity of COVID-19 and other infectious and non-infectious pathologies. When analyzing the esterase status of blood plasma, the esterase activity of serum albumin, which is the major protein in the blood of mammals, should not be ignored. The purpose of this study is to expand understanding of the esterase status of blood plasma and to evaluate the relationship of the esterase status, which includes information on the amount and enzymatic activity of human serum albumin (HSA), with other biochemical parameters of human blood, using the example of surviving and deceased patients with confirmed COVID-19. In experiments in vitro and in silico, the activity of human plasma and pure HSA towards various substrates was studied, and the effect of various inhibitors on this activity was tested. Then, a comparative analysis of the esterase status and a number of basic biochemical parameters of the blood plasma of healthy subjects and patients with confirmed COVID-19 was performed. Statistically significant differences have been found in esterase status and biochemical indices (including albumin levels) between healthy subjects and patients with COVID-19, as well as between surviving and deceased patients. Additional evidence has been obtained for the importance of albumin as a diagnostic marker. Of particular interest is a new index, [Urea] x [MDA] x 1000/(BChEb x [ALB]), which in the group of deceased patients was 10 times higher than in the group of survivors and 26 times higher than the value in the group of apparently healthy elderly subjects.Item Open Access Albumin is an integrative protein of blood plasma and beyond.(MDPI, 2024-11-25) Belinskaia, D. A.; Jenkins, R. O.; Goncharov, N. V.Item Metadata only An algorithm for deriving new combinatorial biomarkers based on ridge regression(Cifra, 2018-02-22) Terpilowski, M. A.; Korf, E. A.; Jenkins, R. O.; Goncharov, Nikolay V.Motivation: Combinatorial biomarkers are considered more specific and sensitive than single markers in medical diagnostics and prediction, yet even detection of such these combinatorial biomarkers requires deep computational analysis. The principles of analytic combinatorics, linear and kernel ridge regression, and machine learning were applied to derive new combinatorial biomarkers of muscle damage. Results: Lactate, phosphate, and middle-chain fatty acids were most often included into biochemical combinatorial markers, while the following physiological parameters were found to be prevalent: muscle isometric strength, H-reflex length, and contraction tone. Several strongly correlated combinatorial biomarkers of muscle damage with high prediction accuracy scores were identified. The approach — based on computational methods, regression algorithms and machine learning — provides a flexible, platform independent and highly extendable means of discovery and evaluation of combinatorial biomarkers alongside current diagnostic tools. Availability: The developed algorithm was implemented in Python programming language on a quantitative dataset comprising 23 biochemical parameters, 37 physiological parameters and 3,903 observations. The algorithm and our dataset are available free of charge on GitHub. Supplementary information: Supplementary data are available at Journal of Bioinformatics and Genomics online.Item Metadata only The analysis of inorganic and methyl mercury by derivatisation methods: opportunities and difficulties.(Elsevier, 1999) Craig, P. J.; Jenkins, R. O.; Stojak, G. H.We discuss three methods of analysis of methyl and inorganic mercury in sediments and water and present new results for one of these. The methods used are (1) solvent extraction and derivatization to CH3HgBr (with separate analysis of inorganic mercury) with determination by electron capture gas chromatography, (2) aqueous phase derivatization using NaB(C2H5)(4) with detection by atomic absorption spectroscopy and (3) derivatization with NaBH4 with detection of CH3Hg and inorganic mercury by atomic absorption and mass spectroscopes. We present new results on the analytical stability of CH3HgH and discuss errors arising in the methodsItem Metadata only The analysis of inorganic and methyl mercury by the derivatisation method: opportunities and difficulties(1999-05) Craig, P. J.; Jenkins, R. O.; Stojack, G. H.Item Metadata only Analysis of organometallic compounds in environment and biological samples.(Royal Society of Chemistry, 2010-01) Harrington, Christopher F.; Vidler, D. S.; Jenkins, R. O.Measurement of the different physicochemical forms of metals and metalloids is a necessary pre-requisite for the detailed understanding of an element’s interaction with environmental and biological systems. Such chemical speciation data is important in a range of areas, including toxicology, ecotoxicology, biogeochemistry, food safety and nutrition. This chapter considers developments in the speciation analysis of organometallic compounds (OMCs), focusing on those of As, Hg, Se and Sn. Typically, organometallic analysis requires a chromatographic separation prior to analyte detection and gas chromatography (GC), high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) can serve this purpose. Following separation, detection is achieved using element specific detectors (ESDs) such as inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectroscopy (ICP-OES), atomic fluorescence spectrometry (AFS), atomic absorption spectrometry (AAS) or atmospheric pressure ionization mass spectrometry (API-MS). Techniques employing a vapor generation (VG) stage prior to detection are also discussed. Complementary structural and quantitative data may be acquired through the combination of elemental and molecular mass spectrometry. The advantages and disadvantages of the various analytical systems are discussed, together with issues related to quantification and quality management.Item Metadata only An analytical method for the detection of methyl antimony species in environmental matrices: methyl antimony levels in some UK plant material.(Royal Society of Chemistry, 1999) Craig, P. J.; Jenkins, R. O.; Forster, S. N.; Miller, D. P.We report, using sodium borohydride (NaBH4) derivatizing agent with purge and trap quartz furnace atomic absorption spectrometry (QF-AAS), a method for the detection of methylantimony compounds from environmental matrices and samples. The generation of trimethylantimony as a standard compound has also been examined using (CH3)(3)SbCl2. This method has been reported previously to produce not only (CH3)(3)Sb but mixtures of (CH3)(2)SbH, CH3SbH2 and SbH3 when solutions of (CH3)(3)SbCl2 were derivatized. Rigorous exclusion of oxygen combined with rapid purging of reduced analytes into a cold trap has reduced these by-products to undetectable levels. These results are of importance in view of the increasing importance of the role of organoantimony species in the natural environment, which depends on the reliability of speciation produced by the hydride generation method. Levels of methylantimony found in some UK plant samples are in the 100-200 ng g(-1) range. This is the first report of methylantimony species from the UK natural environment.Item Metadata only Antibiotic susceptibility including tigecycline and MALDI-TOF MS of E. coli and S. aureus isolates(2010-06) Chiriseri, E.; Jenkins, R. O.; Minassian, M. A.Item Open Access Anticancer drug cytotoxicity assessed using controllable HELA TET-ON/HCYP1 cell lines(2016-04) Jenkins, R. O.; Li, N-G; Goncharov, Nikolay V.Objective: P450 enzymes have a key role in the metabolism of a many anticancer drugs. Metabolism via CYP1s in a variety of solid tumours is thought to aid tumour avoidance of chemotherapeutic induced cytotoxicity. The objective of the present research was to establish the influence of CYP1 mediated metabolism of three anticancer drugs (baicalein, resveratrol, doxorubicin) on their cytotoxicity, using a series of HeLa Tet-ON/hCYP1 cell lines controllably expressing CYP1 enzymes. Methods: The full length genes coding human CYP1A1, CYP1A2 and CYP1B1 were cloned from human liver cDNA library by PCR into the cloning plasmid pBluescriptKS(+) and expressed in different mammalian vectors, with subsequent DNA sequencing of the cloned CYP1 genes. The cytotoxicity of the anticancer drugs (baicalein, resveratrol, doxorubicin) by CYP1 cells was investigated in the presence and absence of α-naphthoflavone (ANF; potent inhibitor of CYP1 family). Cell survival was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results: CYP1A1 was found to be the most potent enzyme for conversion of the anticancer drugs to more cytotoxic metabolites. CYP1A1, but not CYP1B1 or CYP1A2, enhanced cytotoxicity of resveratrol. Doxorubicin was found to have highest increase (53-fold) in cytotoxicity mediated by CYP1A1 (Table 1 and Fig. 1). Conclusion: Tumours expressing CYP1A1 would respond more favourably to doxorubicin and could be treated effectively with lower doses of the anticancer agent, thus reducing harm to normal tissue. The double stable cell lines expressing CYP1 enzymes were effective cellular systems for assessing cytotoxicity profiles of candidate anticancer agents.Item Metadata only Antimonate-respiration by anaerobic bacteria of environmental origin(2003-12) Hartmann, L. M.; Craig, P. J.; Jenkins, R. O.Item Metadata only Antimony and SIDS: Is there a role for Scopulariopsis brevicaulis?(1997-12) Jenkins, R. O.Item Metadata only Antimony biomethylation by an aerobic bacterium: Flavobacterium sp.(Springer, 2002) Jenkins, R. O.; Forster, S. N.; Craig, P. J.Item Metadata only Antimony biomethylation by mixed-cultures of microorganisms under anaerobic conditions.(Wiley, 1998) Jenkins, R. O.; Craig, P. J.; Miller, D. P.; Stoop, L. C. A. M.; Ostah, N.; Morris, T-AThe volatile antimony compound trimethylantimony (TMA) was detected in headspace gases over anaerobic soil enrichment cultures spiked with potassium antimony tartrate. The presence of TMA was variable (12 positives from 104 cultures) and dependent upon both the inoculum source (environmental sample) and enrichment culture conditions. Positives for TMA formation were obtained with variable frequency for four of the six soils tested and for three types of enrichment culture, designed to encourage growth of nitrate-reducing, methane-producing or fermentative bacteria. The identity of the volatile antimony compound produced in each of the three types of enrichment culture was confirmed by gas chromatography-mass spectrometry and gas chromatography-atomic absorption spectroscopy. There was no evidence of any other volatile antimony compound in the headspace gases. These data suggest that the capability to generate TMA is widely distributed in the terrestrial environment and is attributable to different metabolic types of micro-organisms.Item Metadata only Antimony in the cot environment and its relevant to sudden infant death syndrome(2001-06) Jenkins, R. O.Item Metadata only Antimony leaching from cot mattresses and sudden infant death syndrome (SIDS)(STOCKTON PRESS, 1998) Jenkins, R. O.; Craig, P. J.; Goessler, W.; Irgolic, K. J.1 Polyvinyl chloride (PVC) cot mattress covers from SIDS cases were investigated as potential sources of soluble (potentially ingestable) antimony in the cot environment. 2 Body fluids (urine, saliva) and proprietary domestic detergents/sterilizing fluids markedly enhanced leaching of antimony from PVC. Release of antimony was also enhanced at both low and high pH and by elevated temperature. The extent of antimony leaching did not correlate well with PVC content of this element. 3 These data do not support the assumption that postmortem analysis of antimony content proves exposure to gaseous antimony trihydride from mattress PVC. 4 Ingestion of antimony released from PVC could account for the high variability associated with reported detectable levels of antimony in liver from both SIDS and other infants. It could also explain suspected additional postnatal exposure to this element, which gives rise to elevated levels of Sb in the hair of some healthy infants.Item Open Access Apoptosis/necrosis ratio in THP-1 cell line (human monocytic leukemia cells) exposed to esters of 2,3-dihydroazete series.(2016-04) Jenkins, R. O.; Kudryavtsev, I.; Serebriakova, M.; Smetanin, I. A.; Agafonova, A. V.; Voitenko, Natalia G.; Trulioff, A.; Goncharov, Nikolay V.Objective: The failure of many anti-cancer chemotherapeutics is due to their inability to induce apoptosis at the cellular level. Many cancers can develop pro-survival adaptations and anti-apoptotic signaling pathways, leading to drug resistance. Development of prodrugs that induce targeted necrosis is one strategy to circumvent apoptosis-resistance. However, we hold the opinion that necrosis should be the natural outcome of primary and fully developed apoptosis, in order to maximally avoid side effects with healthy tissues at the stage of preclinical and clinical studies. Recently we developed two two-step procedures for the synthesis of thermally and hydrolytically stable 2,3-dihydroazete-2,3-di-/2,2,3-tricarboxylates (2,3-dihydroazetes) [in press]. The objective of the present research was to assess their pro-apoptotic and/or pro-necrotic abilities with cell suspension culture of human monocytic leukemia cells (THP-1), along with their general cytotoxic effect. Methods: Cultivation of the THP-1 cell line was in supplemented RPMI-1640 medium. For assessment of cell viability, two DNA binding dyes - YO-PRO-1 and propidium iodide (PI) - were used (‘normal’cells, not stained; cells at early stages of apoptosis, YO-PRO-1 positive; cells at later stages, YO-PRO-1 and PI positive). Results: 2,3-Dihydroazetes tested over the range 10-5 to 2×10-4 M showed significant differences in their ability not only to induce the cell death, but also in the way they do so by inducing predominantly apoptosis or necrosis. To adequately describe and quantitatively assess their apoptotic and/or necrotic potential, on one hand, and their general cytotoxic potential, on the other hand, we took the difference between the two areas under the curves, apoptotic and necrotic, over the concentration range. Dihydroazete 2a exhibited the maximal apoptotic/necrotic difference with the THP-1 cell line (Figs. 1, 2); 2m,n,k showed a lower and non-significant difference due to higher necrotic potential at nearly the same cytotoxicity as 2a; dihydroazetes 2b,e and 8a showed a lower though significant difference due to higher necrotic potential coupled with a lower cytotoxicity; 2h had both a very low difference and a very low cytotoxicity, and dihydroazetes 8g,c exhibited a negative difference due to predominantly necrotic cell death at a moderate to high level of cytotoxicity. Figure 1. The quantitative estimates of the apoptotic/necrotic difference (AND) of the dihydroazetes 2a,b,e,h,k,m,n and 8a,c,g exhibited with the THP-1 cell line. *) Р<0.05 Figure 2. Concentration dependency (C = mole × L-1) of apoptosis and necrosis induction. Percentage of dead cells as determined by DNA binding dyes YO-PRO-1 and PI via flow cytometry after treatment of THP-1 cells for 24 h with different concentrations of 2a. Conclusion: The newly synthesized thermally stable 2,3-dihydroazetes greatly differ in their ability to induce apoptosis and/or necrosis, and could be good candidates for further studies of their anti-cancer activities.Item Metadata only Application of a low-angle light scattering technique to cell volume and cell signaling studies on Ehrlich ascite tumor cells.(ISO Press, 2006) Zinchenko, V. P.; Lee, V. V.; Berezhnov, V. A.; Mindukshev, I. V.; Jenkins, R. O.; Goncharov, Nikolay V.