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Thymidine kinase 1 (TK1) is converting thymidine to thymidine monophosphate, and is related to DNA replication and cell proliferation. The use of the TK1 protein levels as a proliferation marker in malignancies is here summarized. TK1 protein in serum (STK1p) and TK1 expression in tissues were determined by a chemoluminescent dot blot assay and by immunohistochemistry staining, respectively. The expression of TK1 in tumor tissues correlated to pathological stages and clinical grades of carcinomas (ca) of esophagus, lung and in premalignancy of breast ductal ca. STK1p could monitor the out-come of tumor therapy by being correlated to remission [breast ca, non-Hodgkin's lymphoma], relapse [breast ca] and to survival [non-Hodgkin's lymphoma] of patients. In a health screening study of 12,641 persons, STK1p seemed to predict the risk of development of neoplasia related diseases at early stage. [ABSTRACT FROM AUTHOR]

Abstract. The effect of radiation on TK is more complicated than would be expected from earlier results on bone marrow cells (Feinendegen et al. 1984, Int. J. Radiat. Biol. 45, 205). TK activity increased at 0.01 Gy and then decreased up to 1 Gy in mouse spleen. In contrast to the results for the spleen, an increase in activity at 0.1 Gy was seen in mouse thymus. The activity of dephosphorylated TK1 (TK1a) in both spleen and thymus was reduced to 50% after irradiation at 0.5–1 Gy. The degree of phosphorylation (TK1b/TK1a ratio) changed in spleen, but not in thymus. The activity of TK2 in mouse liver increased at 3 h after 5 Gy by about 60%. In mouse ascites tumour, a dose-independent (1–5 Gy) oscillating TK1 activity was found up to 24 h, especially for TK1a and TK1b. The amount of TK1 was unchanged up to 12 h, but decreased at 24 h. This suggests that the differences in the changes in the degree of phosphorylation of TK1 after irradiation among spleen, thymus and ascites tumour further underline the complexity of the response of TK1 activity to irradiation. The dramatic change in the activities of TK1a and TK1b may illustrate that both of them are more radiosensitive than TK-h, a variant with mixed TK1 and TK2 properties. [ABSTRACT FROM AUTHOR]

Abstract. The purpose of this study was to investigate the mechanism behind the high sensitivity of thymidine kinase 1 (TK1) to X-irradiation. The deoxythymidine triphosphate (dTTP) pool was studied in mouse ascites tumour cells 1–24 h after X-irradiation with 5 Gy. Irradiation changed the Michaelis-Menten kinetics of TK1 from linear to biphasic, showing a negative co-operativity. These changes were closely related to changes in the dTTP pool. Addition of dTTP to the cell extract of non-irradiated cells, or thymidine (dTdR) to the culture medium, resulted in changes very similar to the kinetics found in the irradiated cells. Addition of 5¢-amino-5¢-deoxythymidine (5¢-AdTdR), a thymidine analogue that eliminated the inhibitory effect of dTTP on TK1 activity, completely abolished the irradiation-induced inhibition of TK1 activity. We suggest that the reduced TK1 activity is mainly due to an elevated intracellular concentration of dTTP. [ABSTRACT FROM AUTHOR]

Abstract. From clinical studies in cancer patients and experimental in vitro studies, there is evidence of an increased cytotoxic effect, and even synergy, when irradiation is combined with 5-fluorouracil (5-FU). The mechanism for this is unclear. Materials and Methods : Mouse fetuses (C3 H) have been exposed in vivo to X-irradiation and 5-fluorouracil (5-FU) as single agents or in combination. Cell proliferation, cell cycle progression, fetal survival and incidence of fetal malformations have been studied. Purpose : The aim of this study was to determine possible synergistic cytotoxic effects when 5-FU and ionizing radiation were combined, particularly concerning the regulation of cell cycle progression in proliferating, non malignant mammalian cells in vivo . Results : The combination of low-toxic doses of X- irradiation and 5-FU had a synergistic toxic effect in nonmalignant mouse fetuses in vivo . The cell cycle regulation was perturbed and the radiation-induced G 2 -arrest was eradicated by 5-FU during the initial hours. Conclusions : The time for repair of radiation induced DNA-damage is probably reduced, which may explain the increased toxicity of this combination. [ABSTRACT FROM AUTHOR]

Abstract. Human DNA-dependent protein kinase (DNA-PK) is a nuclear-localized serine/threonine protein kinase. The holoenzyme consists of a catalytic subunit with a molecular mass of 465 kDa and a DNA-binding heterodimer Ku86/70. The kinase has been implicated in a variety of nuclear processes including V(D)J recombination, double-strand break repair, and transcription. Cells with defective DNA-PK activity show increased radiosensitivity and lack of V(D)J recombination. To study DNA-PK activity during the cell cycle, HeLa cells were separated by elutriation centrifugation into different cell cycle compartments based on cellular size. DNA-PK activity was found to vary during the cell cycle. The kinase activity was lowest during G1 phase and increased dramatically as the cells entered S phase and remained high during the G2-phase. The subcellular distribution of DNA-PKcs is relocalized from the cytoplasm during M and G1 phases to the nucleus during G1–S phase transition and S phase. Expression of both the catalytic subunit and the Ku86/70 heterodimer was found to be constant throughout the cell cycle. This study demonstrates that DNA-PK activity as well as its subcellular localization fluctuates during the cell cycle. In addition, the distribution of DNA-PK during M phase corresponds with low DNA-PK activity. [ABSTRACT FROM AUTHOR]

Reasons for performing study Cervical spine lesions are often suspected in horses with neurological signs, abnormal head/neck position and obscure forelimb lameness. Computed tomography ( CT) has the potential to image the cervical spine in 3 dimensions in superior anatomical detail; e.g. lesions that cause compression of the spinal cord and nerve roots, small fragments, and osteoarthritis of the articular process joints may be more easily detected. Objectives To investigate if CT and CT myelography of the entire cervical spine is possible in horses, describe the technique used, the type of horses and distribution of cervical lesions detected. Study design Retrospective case series. Methods Horses undergoing cervical CT and CT myelography from June 2013 to February 2014 were reviewed. The horses were anaesthetised in left lateral recumbency using continuous intravenous anaesthesia. A Philips Brilliance Big Bore 16 slice scanner and a custom made equine CT table (Solving, Finland) were used. Results Cervical CT was performed on 16 horses, 11 of which also had CT myelography: 12 Warmblood, 2 ponies, 1 Standardbred and 1 Paint Horse. Horses ranged in age from 1 to 21 years, and in weight from 406 to 670 kg. Presenting complaints were: neurological symptoms (n = 8), abnormal head/neck position (n = 5), forelimb lameness (n = 4), Horners syndrome (n = 1). In all cases (n = 16) the cervical spine from the skull to C7 could be imaged, in 3 cases T1 was imaged and in one case T3. Significant lesions were detected in 14 horses. The sites of the most significant lesions were: C4- C5 (n = 3), C5- C6 (n = 2), C6- C7 (n = 5) and C7- T1 (n = 2), cervical stenosis C5- T2 (n = 1) and muscle injury (n = 1). Length of anaesthesia ranged from 35 to 70 min (median 60 min), with one complicated recovery. Conclusions Cervical CT and CT myelography can be performed in large adult horses. CT may be the future gold standard to evaluate equine cervical lesions. Further studies are needed. Ethical animal research: Ethical committee oversight not currently required by this congress: retrospective study of clinical records. Explicit owner informed consent for participation in this study was not stated. Sources of funding: None. Competing interests: None. [ABSTRACT FROM AUTHOR]

As part of an extensive audit of the Alkaline-Peroxide Mechanical Pulping (APMP(TM)) plant at the Malette Quebec Inc. mill in St. Raymond, Que., effluents were sampled from various stages of the process forcomprehensive chemical characterizations, aquatic toxicity testing and anaerobic biotreatability assessments. In addition, untreated andsecondary treated combined effluent from the integrated paper mill were sampled to determine the effectiveness of a conventional activated sludge process at the mill site. During the one-day sampling period, the APMP plant processed a mixed wood furnish consisting of 50% spruce/balsam fir and 50% aspen, with a chemical charge of 3.5% sodium hydroxide and 3.8% hydrogen peroxide on oven-dry fibre, while the Machine Finish Coated (MFC) paper production rate was 100 odt/d (oven dry metric tonnes per day). Measured production-specific contaminant discharge loadings from the novel APMP process were 56 kg BOD {sub}5{end}/odt and 155 kg COD/odt in a combined effluent flow of 28 m {sup}3 end}/odt. Sources of process effluent were chip washing, three stages of wood chip pretreatment and chemical impregnation (i.e., Impressafiner stages), interstage washing and pulp cleaning. The three Impressafiner pressates were found to be the most concentrated (i.e., 12--26 g COD/L) and toxic streams. Microtox testing of the pressates revealed EC {sub}50{end} concentrations of 0.07- -0.34% v/v. The warm and concentrated effluents generated by the non-sulphur APMP process were found to be highly amenable to anaerobic degradation as determinedby batch bioassay testing. Filterable BOD{sub}5{end} and COD(f) of the process effluents were reduced by 87--95% and 70--77%, respectively, with corresponding theoretical methane yields being attained. Acid-soluble dissolved lignin compounds exhibited biorecalcitrance, as revealed by limited removals of 34--55%, and were the main constituents contributing to residual COD(f), while resin and fatty acids (RFA) wer [ABSTRACT FROM AUTHOR]