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  • Springer  (300)
  • 1
    ISSN: 1420-9071
    Keywords: Key words. Two-dimensional gel electrophoresis; mass spectrometry; cell transformation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Signalling via the protein kinase Raf-MEK-ERK pathway is of major importance for transformation by oncogenes. To identify genes affected by inhibition of this pathway, c-JUN transformed rat fibroblasts were treated with a MEK1 inhibitor (PD98059) and subjected to two-dimensional gel electrophoresis after cell lysis. Gene products with expression influenced by MEK1 inhibition were determined by mass spectrometry of fragments from in-gel tryptic digestions. The expression of pirin, a nuclear factor I-interacting protein, was lowered after inhibition of MEK1. Western blot analysis revealed increased expression of pirin in RAS and c-JUN transformed cells in the absence of PD98059. Inhibition of MEK1 also led to reduced expression of α-enolase, phosphoglycerate kinase, elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3, the latter two being detected as truncated proteins. In contrast, the level of ornithine aminotransferase was increased. We conclude that inhibition of MEK1 results in major alterations of protein expression in c-JUN transformed cells, suggesting that this pathway is important for oncogene-induced phenotypic changes.
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  • 2
    ISSN: 1432-1424
    Keywords: Na-gradient coupled transports ; amino acid transports ; electrogenic transports ; epithelial cells ; Xenopus laevis embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The electrical responses induced by external applications of neutral amino acids were used to determine whether different carriers are expressed in the membrane of embryonic epithelial cells ofXenopus laevis. Competition experiments were performed under voltage-clamp conditions at constant membrane potential. Gly,l-Ala,l-Pro,l-Ser,l-Asn andl-Gln generate electrical responses with similar apparent kinetic constants and compete for the same carrier. They are [Na] o and voltage-dependent, insensitive to variations in [Cl] o and [HCO3] o , inhibited by pH o changes, by amiloride and, for a large fraction of the current, by MeAIB. The increase in [K] o at constant and negative membrane potential reduces the response, whereas lowering [K] o augments it. l-Leu,l-Phe andl-Pro appear to compete for another carrier. They generate electrogenic responses insensitive to amiloride and MeAIB, as well as to alterations of membrane potential, [Na] o and [K] o . Lowering [Cl] o decreases their size, whereas increasing [HCO3] o at neutral pH o increases it. It is concluded that at least two and possibly three transport systems (A, ASC and L) are expressed in the membrane of the embryonic cells studied. An unexpected electrogenic character of the L system is revealed by the present study and seems to be indirectly linked to the transport function. l-Pro seems to be transported by system A or ASC in the presence of Na and by system L in the absence of Na. MeAIB induces an inward current.
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  • 3
    ISSN: 1573-4943
    Keywords: Capillary electrophoresis ; peptides ; micropreparation ; matrix-assisted laser desorption/ionization mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Signal suppression is a problem in matrix-assisted laser desorption/ionization mass spectrometry of peptides prepared by capillary electrophoresis. Many common electrolytes that are efficient for separation, such as sodium phosphate, also are strongly suppressive during laser desorption/ionization. We have tested individual electrolytes for highest performance in each step of separation and collection, respectively. Suppression is not observed if citrate, trifluoroacetic acid, or hydrochloric acid is used for collection, while phosphate still can be employed in the capillary providing excellent resolution. Low concentrations of hydrochloric acid added to the sample/matrix mixture generate mass spectra with better ion intensities than if trifluoroacetic acid or citrate is used.
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  • 4
    ISSN: 1432-1041
    Keywords: Digoxin ; diuretics ; drug compliance ; drug utilization ; intoxication ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma digoxin was measured in all patients receiving digoxin (Lanacrist, Draco) in a well-defined low density population area in Sweden. The number of treated patients (n=75) corresponded to 3 % of the population. The average prescribed daily dose of digoxin was 0.25 mg, and the mean plasma concentration (n=74) was 0.85 (S.D. 0.52) ng/ml. Of the concentrations found 3 % were above and 62 % were below the apparent therapeutic range, 1 – 2 ng/ml. The findings were compared with analyses performed in a hospital laboratory (n=300), the majority being inpatients receiving a similar daily dose. In the latter, 22 % had a plasma level above and about 33 % below the apparent therapeutic range. In the former group no difference in plasma digoxin concentration could be demonstrated between patients treated with digoxin (n=34) and those treated with both digoxin and diuretics (n=40). In a group of eight patients plasma digoxin rose significantly after they were informed of the importance of taking their medicine regularly. Poor compliance with prescribed therapy was even documented in patients in cardiac failure.
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  • 5
    ISSN: 1432-1041
    Keywords: prescribing habits ; psychotropics ; drug utilization ; methodology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The prescription of psychotropic drugs at a multidoctor district health centre in northern Sweden in 1973, was analysed by means of problemoriented medical records. Of the 22,000 inhabitants of the district 10,700 consulted the health centre. Psychotropic drugs were prescribed for 11.3% of the patients, corresponding to 5% of the inhabitants of the area. Sixty per cent of the patients received one psychotropic prescription and 90% not more than three. Two-thirds of prescriptions were for women. Hypnotics, sedatives and minor tranquillisers constituted 64% of all prescriptions, major tranquillisers 24% and antidepressants 12%. One fifth of the patients obtained drugs belonging to more than one of the major psychotropic groups during the year. Insomnia, psychoneurosis and depression made up two-thirds of the indications for psychotropic drug therapy. More than thirty different psychotropic drugs were prescribed for the two major indications. There was considerable variation in how the different doctors prescribed drugs for the same indication. Fifty-nine different drug products were prescribed, of which the commonest five constituted more than half of the total number. Individual doctors used from 22 to 38 different psychotropic drugs.
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  • 6
    ISSN: 1432-1041
    Keywords: drug utilisation ; prescribing habits ; hypnotics ; sedatives ; minor tranquillisers ; defined daily doses ; therapeutic audit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The utilisation of hypnotics, sedatives, and minor tranquillisers (HSmT) was studied by means of drug-delivery and hospital occupancy statistics for 1975–1977 in a Swedish university hospital. A total of 0.53 so-called defined daily doses (DDD)/bed-day were delivered in 1975, implying that every second patient might have regularly been prescribed HSmT. The benzodiazepines were predominant with 71% of the deliveries. Five major drugs accounted for 88%. The drug pattern and the range of DDD/bed-day (0.09–1.18) differed considerably between the departments. Drugs not recommended by the hospital's Pharmacy and Therapeutics Committee accounted only for 3% of deliveries. In a drug surveillance study performed in two medical wards, HSmT were prescribed for 43% of 274 patients. Drug delivery and prescription data were in broad agreement. Drug information activities in the hospital had a clearly discernable influence on the delivered DDD/bed-day. This measure is an inexpensive indicator of drug utilisation in a hospital and a suitable basis for therapeutic audit.
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  • 7
    ISSN: 1432-1041
    Keywords: drug problems ; patient compliance ; adverse drug reactions ; interview ; pharmacokinetics ; inadequate therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The association between hospital admission and drug-related problems was evaluated in 285 consecutive admissions to two medical wards in a Swedish university hospital. Standardised definitions and criteria for causality were used. A drug-related problem was judged to have been the main reason for admission of 36 patients, and a strongly contributory reason for 9. These 45 patients comprised 16% of all patients, and 19% of those receiving medication prior to admission. For 19 patients the problem was considered to be failure to achieve the desired therapeutic effect. 11 of these 19 took less medication than prescribed, and an inadequate dose had been presented for the other 8 patients. In 26 patients there was an excessive or otherwise adverse effect. In 10 it was an intentional or accidental poisoning, and 16 had an adverse drug reaction. Non-compliance with the prescribed regimen caused almost half of the drug-related admissions: 11 took too little and 10 took too much of the prescribed drugs. The majority of the other problems could probably have been prevented by better application of pharmacokinetic principles to the prescribing.
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  • 8
    ISSN: 1432-1041
    Keywords: drug epidemiology ; prescription forgeries ; substance abuse ; psychotropic drugs ; analgesics ; benzodiaepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Data on forged prescriptions in Sweden in 1982–1986 were studied as an indicator in an epidemiological survey of medication abuse. The annual number of prescription forgeries doubled during the 5-year period. Psychotropic drugs accounted for 62% and analgesics for 25% of all forgeries. Benzodiazepines were the major single drug group, comprising 52% of all forgeries during the period. The major benzodiazepines on the market in Sweden (diazepam, oxazepam, nitrazepam and flunitrazepam) were the subject of largest number of forgeries. When calculated in relation to the utilization (either total sales or the number of prescriptions), the analgesics codeine, pentazocine and ketobemidone were clearly at the head of the list, suggesting greater abuse liability of these drugs. It is suggested that the data on forged prescriptions can be used as a “signalling mechanism” in epidemiological surveillance of medication abuse, aimed at detecting changes in the prevalence as well as in the pattern of abuse.
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  • 9
    ISSN: 1432-1041
    Keywords: Psychotropic drugs ; drug utilisation ; geographical differences ; prescribing habits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Marked differences in the utilisation of psychotropic drugs between the three major urban areas in Sweden were recorded from four sources of information: drug supplies from wholesalers to pharmacies, drug supplies to hospitals for in-patient use, drugs sold on prescription for out-patient use, and out-patient consultation and drug prescribing as recorded by physicians. The total sales of psychotropics in the counties of Gothenburg (110,8 defined daily doses per 1000 inhabitants per day) and Malmö (102,1) were much higher than in the county of Stockholm (73,4), with about 25% of the difference being accounted for by diazepam. Differences in the total sales of psychotropics were not explained by any differences in hospital sales, which amounted to about 10% in all counties. Prescription sales differed due to the higher average number of DDD (defined daily doses) per prescription in Gothenburg and Malmö than in Stockholm (total psychotropics 8 and 15%, respectively), and especially because of the higher number of prescriptions per inhabitant (about 40 and 30–35%, respectively). There was no substantial difference in the pattern of diagnoses between areas, but there was a noticeable difference with regard to prescriber category, as psychiatrists accounted for more of the prescriptions in Stockholm than in Gothenburg and Malmö. The results raise questions about over- and under-treatment of mental disorders and about abuse of drugs. In order to explain the geographical differences in psychotropic drug sales morbidity patterns and prescribing practices should be further explored.
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  • 10
    ISSN: 1432-072X
    Keywords: Anabaena ; Cyanobacteria ; Ammonium release ; Photorespiration ; Glycollate pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A release of ammonium by non-nitrogen-fixing Anabaena cylindrica (grown on NH4Cl) in the presence of MSX (methionine sulfoximine) and absence of any external nitrogen source was found. In the light the release was maximal at 0.2 mM MSX, a concentration which did not affect net CO2 fixation nor the glycollate excretion, but inhibited the glutamine synthetase activity and the reassimilation of ammonium. It is suggested that the major source of the ammonium released is the photorespiratory conversion of glycine to serine as (1) the release was stimulated by increase in light intensity, (2) high CO2 (3%) lowered the release, if not given as a longer pretreatment (as CO2 or HCO 3 - ) when a stimulation was observed, (3) glyoxylate and glutamate stimulated the release, the latter compound particularly under nitrogen-deficient conditions and (4) isonicotinic acid hydrazide caused a reduced release of ammonium. Furthermore, a substantial part of the ammonium released by N2-fixing A. cylindrica in presence of MSX may thus originate from the glycollate pathway. The data show that in the light the glycine to serine conversion is active in cyanobacteria with a concomitant production of ammonium which is assimilated by glutamine synthetase.
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