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81.
Sørensen NM Kobaek-Larsen M Bonne A van Zutphen B Fenger C Kristiansen K Ritskes-Hoitinga M 《Comparative medicine》2003,53(6):633-638
The aim of the study reported here was to investigate whether the azoxymethane (AOM)-induced colon cancer rat model mimics the human situation with regard to microsatellite stability, changes in expression of beta-catenin, and/or changes in the sequence of the proto-oncogene Ki-ras. Colon cancer was induced by administration of four weekly doses of AOM (15 mg/kg of body weight per week) separated by a one-week break between the second and third injections. As the histopathologic characteristics of this model resemble those of the human counterpart, further characterization of the genetic changes was undertaken. The animals were euthanized 28 to 29 weeks after the first AOM injection, and tumor specimens were taken for histologic and DNA analyses. Since microsatellite variation was found in only a few (< 2%) specimens, the model can be considered as having stable microsatellites. This result is in accordance with those of similar studies in other rat models and with most human colorectal cancers. Immunohistochemical analyses of beta-catenin did not reveal loss of gene activity, nor did the sequencing of Ki-ras reveal mutations. These results are in contrast to most findings in comparable rat studies. The deviations may be due to differences in exposure to the carcinogen or difference in strain and/or age. The lack of beta-catenin and Ki-ras alterations in this colon cancer model is unlike human sporadic colorectal cancers where these genetic changes are common findings. 相似文献
82.
83.
Morten Miller Ansa Paloj?rvi Andrea Rangger Morten Reeslev Annelise Kj?ller 《Applied and environmental microbiology》1998,64(2):613-617
Our objective was to determine if 4-methylumbelliferyl-labelled enzyme substrates could be used to detect and quantify specific components of chitinase and cellulase activities as specific indicators of the presence and activity of fungal biomass. The fluorogenic substrates 4-methylumbelliferyl (MUF) N-acetyl-β-d-glucosaminide and MUF β-d-lactoside were used for the detection and quantification of β-N-acetylglucosaminidase (EC 3.2.1.30) (NAGase) and endo 1,4-β-glucanase (EC 3.2.1.4)/cellobiohydrolase (EC 3.2.1.91) (CELase), respectively. Culture screenings on solid media showed a widespread ability to produce NAGase among a taxonomically diverse selection of fungi on media with and without added chitin. NAGase activity was expressed only in a limited number of bacteria and on media supplemented with chitin. The CELase activity was observed only in a limited number of fungi and bacteria. Bacterial CELase activity was expressed on agar media containing a cellulose-derived substrate. In soil samples, NAGase activity was significantly correlated with estimates of fungal biomass, based on the content of two fungus-specific indicator molecules, 18:2ω6 phospholipid fatty acid (PLFA) and ergosterol. CELase activity was significantly correlated with the PLFA-based estimate of fungal biomass in the soil, but no correlation was found with ergosterol-based estimates of fungal biomass.The determination of enzyme activities is a simple approach to the study of microbially mediated processes within the soil environment. Thus, soil enzyme activities have been interpreted as indirect measures of microbial biomass, rhizosphere effects, soil productivity, and mineralization potential of naturally occurring substrates or xenobiotics (4). However, few studies have attempted to correlate soil enzyme activities with the presence and activities of specific components of the microbial community. The ability of soil-inhabiting fungi to produce a range of enzymes capable of degrading complex litter substances could make the use of an enzymatic approach to study soil fungal populations possible. These enzymes must be specific for fungal presence and activity. In one study of chitinase in soil (24), chitinase activity and the number of fungal propagules in chitin-amended soils were strongly correlated. The same correlation was not found for actinomycetes or bacteria. Thus, chitinase activity appears to be a suitable indicator of actively growing fungi in the soil. The hydrolysis of cellulose requires the interaction of a number of hydrolases produced by cellulolytic microorganisms. A major role is played by the cellulase system, which consists of several distinct enzymes that are produced by a large number of microorganisms, including fungi, actinomycetes, and bacteria. However, fungi have been suggested as the predominant source of β-d-glucosidase (EC 3.2.1.21) (16, 17) and endo 1,4-β-glucanase (EC 3.2.1.4) (23) activity in soils.Fluorogenic 4-methylumbelliferyl (MUF)-labelled enzyme substrates have been introduced for process-oriented studies in aquatic systems (3, 18) and, more recently, in peatlands (11). MUF substrates have been used to assay cell-bound activities in pure cultures of fungi, as the soluble substrate can enter the cell wall, making periplasmic enzyme activity detectable (15). These substrates have been used to detect fungal chitinolytic activities (17a) and cellulases (6) in vitro. The substrates may be added to environmental samples and, when hydrolyzed, release 4-methyl-umbelliferone (4-MU), which fluoresces and can be quantified in nanomolar concentrations (3).A variety of methods to quantify fungi in soil have been described. The techniques include direct microscopic observation and extraction of fungus-specific indicator molecules such as glucosamine or ergosterol (9). More recently, the phospholipid fatty acid (PLFA) 18:2ω6 has been proposed as an indicator of fungal biomass (7, 12). Our objectives in the present study were to determine if (i) components of chitinase and cellulase activities could be used as indicators of the presence and activity of fungal biomass and (ii) enzyme activities detected with specific MUF substrates in soil samples were correlated with the content of the fungus-specific indicator molecules 18:2ω6 PLFA and ergosterol. 相似文献
84.
Objective: Five years after its introduction, to evaluate the 1992 reform in the out of hours service in Denmark. Design: Comparison of data before and after reform. Data were collected from published reports, Danish national health statistics, and the Danish trade union for general practitioners. Setting: Denmark. Main outcome measures: Number of out of hours services; workload of general practitioners; cost of the service; patient satisfaction. Results: Five years after the reform, the percentage of telephone consultations had almost doubled, to 48%. Consultations in doctors’ surgeries were relatively unchanged, but home visits were much reduced, to 18%. The percentage of doctors who worked 5 hours or more out of hours per week dropped from about 70% to about 50%. Overall patient satisfaction in 1995 was high (72%). Conclusion: The organisation of the out of hours service, with a fully trained general practitioner in a telephone triage function, is working satisfactorily. Many calls that previously would have required home visits are now dealt with by telephone or through consultations. The out of hours workload for general practitioners has decreased considerably.
Key messages
- The out of hours reform in Denmark has resulted in an organisation with a fully trained general practitioner performing the telephone triage function
- Hours on call for general practitioners have decreased considerably
- Home visits have largely been replaced by telephone consultations
- Patient satisfaction has declined slightly
85.
Morten Sandvik 《Biomarkers》1998,3(6):399-410
Absorption and tissue distribution of benzo\[ a ]pyrene (BaP)-derived radioactivity were studied in juvenile rainbow trout following dietary or waterborne exposure. In order to compare the bioavailability of BaP, the fish were exposed to 1.5 mCi 3H-BaP kg-1 fish, either in the diet or in the water as a 2 days static exposure. Furthermore, tissue levels of BaP-derived radioactivity bound to macromolecules in different tissues were studied in non-induced fish, and in fish induced by additional treatment with unlabelled BaP (corresponding to 5 mg kg-1 fish) in the water. Absorption and tissue distribution of 3H BaP were studied by liquid scintillation counting and whole-body autoradiography. BaPderived radioactivity bound to macromolecules in different tissues was studied by autoradiography of solvent-extracted whole-body sections. The hepatic CYP1A induction was measured as EROD activity. Exposure to unlabelled BaP resulted in a marked induction of hepatic EROD activity in rainbow trout 2 days after the start of the exposure. Significant higher concentrations of radiolabelled compound were observed in waterborne-exposed fish, in contrast to dietary-exposed fish. High concentrations of radiolabelling were observed in the gills, liver, bile, intestines, olfactory organ, kidney and the skin of the waterborne-exposed fish. In the dietary-exposed fish, high levels of radioactivity were observed in the intestines and the bile, whereas lower concentrations were present in the liver. Only traces of radioactive compound were observed in the gills. In contrast to waterborne-exposed fish, no radioactivity was detected in the olfactory organ or skin. In autoradiograms of sections extracted with a series of polar and non-polar solvents, a large fraction of radioactivity was still present in the gills, olfactory organ, liver, kidney, skin and intestinal mucosa of the waterborne-exposed fish, indicating that reactive BaP intermediates formed by CYP1A-mediated metabolism were bound to macromolecules in these tissues. 相似文献
86.
Analysis of mannose selection used for transformation of sugar beet 总被引:39,自引:0,他引:39
Joersbo Morten Donaldson Iain Kreiberg Jette Petersen Steen Guldager Brunstedt Janne Okkels Finn T. 《Molecular breeding : new strategies in plant improvement》1998,4(2):111-117
Various factors affecting mannose selection for the production of transgenic plants were studied using Agrobacterium tumefaciens-mediated transformation of sugar beet (Beta vulgaris L.) cotyledonary explants. The selection system is based on the Escherichia coli phosphomannose isomerase (PMI) gene as selectable gene and mannose as selective agent. Transformation frequencies were about 10-fold higher than for kanamycin selection but were only obtained at low selection pressures (1.0–1.5 g/l mannose) where 20–30% of the explants produced shoots. The non-transgenic shoots were eliminated during the selection procedure by a stepwise increase in the mannose concentration up to 10 g/l. Analysis of the transformed shoots showed that the PMI activity varied from 2.4 mU/mg to 350 mU/mg but the expression level was independent of the selection pressure. Complete resistance to mannose of transformed shoots was observed already at low PMI activities (7.5 mU/mg). Genomic DNA blot analysis confirmed the presence of the PMI gene in all transformants analysed. The possible mode of action of mannose selection compared to other selection methods is discussed. 相似文献
87.
Matthew L. Read Morten Brændvang Pedro O. Miranda Lise-Lotte Gundersen 《Bioorganic & medicinal chemistry》2010,18(11):3885-3897
Pyrimidine analogs of antimycobacterial 6-aryl-9-benzylpurines have been synthesized and screened for antibacterial activity against Mycobacterium tuberculosis H37Rv in vitro. Several active compounds were identified and the best results were observed for 5-formamidopyrimidines. These compounds generally displayed IC90 values ≤1 μg/mL, and they exhibited low toxicity towards mammalian cells. Imidazolylpyrimidines, which may be regarded as fleximer analogs of the parent purines, were also synthesized and one of them was found to be quite a potent inhibitor of M. tuberculosis (IC90 14 μg/mL). 相似文献
88.
Torbjrn Jurvi
yvind Wals Morten Barken 《Ethology : formerly Zeitschrift fur Tierpsychologie》1987,76(4):334-342
The ‘social control’ and ‘incongruence’ hypotheses, first put forward by ROHWER (1977) to explain how attempted ‘deceit’ status signalling is kept in check among winter-flocking birds, were tested under semi-natural conditions for Parus major. This species signals its social status by the width of its breast stripe. The lowest-ranked male in experimental flocks, each made up of four individuals, was manipulated in one of three ways: 1) the status signal was altered by painting the breast stripe to make it broader; 2) agonistic behaviour was altered by injecting testosterone; 3) both status signal and behaviour were manipulated. A study of the outcome of subsequent agonistic encounters by these birds revealed that the status of the manipulated individuals only rose when both their behaviour and status signal were altered. This indicates that the ‘social control’ hypothesis must be rejected, but not the ‘incongruence’ hypothesis. 相似文献
89.
Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis 下载免费PDF全文
Ann C. Kroksveen Jacob D. Jaffe Elise Aasebø Harald Barsnes Yngvild Bjørlykke Diego Franciotta Hasmik Keshishian Kjell‐Morten Myhr Jill A. Opsahl Vincent van Pesch Charlotte E. Teunissen Øivind Torkildsen Rune J. Ulvik Heidrun Vethe Steven A. Carr Frode S. Berven 《Proteomics》2015,15(19):3361-3369
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing‐remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase‐3‐like protein 1, secretogranin‐1 (Sg1), cerebellin‐1, neuroserpin, cell surface glycoprotein MUC18, testican‐2 and glutamate receptor 4. An independent sample set of 13 early‐MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early‐MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease. 相似文献
90.
Karin A. W. Wadt Lauren G. Aoude Lotte Krogh Lone Sunde Anders Bojesen Karen Gr?nskov Nine Wartacz Jakob Ek Morten Tolstrup-Andersen Mette Klarskov-Andersen ?ke Borg Steffen Heegaard Jens F. Kiilgaard Thomas V. O. Hansen Kerenaftali Klein G?ran J?nsson Krzysztof T. Drzewiecki Morten Dun? Nicholas K. Hayward Anne-Marie Gerdes 《PloS one》2015,10(3)
Both environmental and host factors influence risk of cutaneous
melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma. 相似文献