| 1. |
- Capala, J, et al.
(author)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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In: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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Journal article (peer-reviewed)abstract
- A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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| 2. |
- Akin, Danny E., et al.
(author)
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Progress in enzyme-retting of flax
- 2004
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In: Journal of Natural Fibers. - 1544-0478. ; 1:1, s. 21-47
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Journal article (peer-reviewed)abstract
- New methods for retting flax are sought to overcome problems in the current method of dew-retting of flax. Published data are reviewed and new data presented on the development and testing of a method to ret flax using pectinase-rich enzyme mixtures plus chelators based on cost and fiber yield and properties. In spray enzyme retting (SER), flax stems are crimped to physically disrupt the plant's protective barrier and then sprayed until soaked with, or briefly immersed in, an enzyme/ chelator formulation. Flax is then incubated at temperatures optimal for enzyme activity, washed, and dried. Pilot scale tests, conducted with 10 kg samples of flax retted with a series of formulations, showed that this method effectively retted flax stems from a variety of sources, including fiber flax, mature fiber flax, and linseed straw. Fiber yield, strength, and fineness were significantly influenced by variations in enzyme-chelator amounts. Cellulases in pectinase mixtures appeared to preferentially attack dislocations in fibers and fiber bundles resulting in loss of fiber strength. Polygalacturonases alone effectively separated fiber from non-fiber components. The SER method proved to be an effective framework for further tests on enzyme-chelator formulations that now must be integrated with physical processing to optimize the extraction of flax fibers based on cost and fiber yield and properties.
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| 3. |
- Asplund, R, et al.
(author)
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Nocturia and depression
- 2004
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In: BJU international. - 1464-4096. ; 93:9, s. 1253-1256
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Journal article (peer-reviewed)
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| 4. |
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| 5. |
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| 6. |
- Frech, Wolfgang, et al.
(author)
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Characterization of a pressurizable two-step atomizer for atomic absorption spectrometry
- 2000
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In: Spectrochimica Acta Part B: Atomic Spectroscopy. ; 55:5, s. 461-72
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Journal article (peer-reviewed)abstract
- A two-step atomizer consisting of a transversely heated atomization tube with integrated contacts and a cup furnace for sample vaporization was constructed. The system could accommodate tubes of various lengths and it could be operated at selected pressures. There was no physical contact between the tube and the cup and mainly diffusion was responsible for the sample vapour transport from the cup to the tube. Under these conditions there was an unavoidable loss by 40% of the peak area signals due to the gap between the cup and the tube. For a 24-mm tube, characteristic masses were on the average three times lower than for the state of the art transverse heated graphite atomizers (THGA). By de-coupling the processes of analyte vaporization and atomization the dynamic working range could be increased by three to six times using conventional measurements by atomic absorption spectrometry (AAS). In this case the cup temperature and hence the rate of analyte transport from the cup to the tube was controlled such that atom density in the tube did not exceed the linear range of the absorbance measurement. Carrying out clean-out steps at reduced pressure decreased memory effects.
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| 7. |
- Gamble, G. R., et al.
(author)
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Phenolic constituents in flax bast tissue and inhibition of cellulase and pectinase
- 2000
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In: Biotechnology letters. - 0141-5492 .- 1573-6776. ; 22:9, s. 741-746
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Journal article (peer-reviewed)abstract
- Flax bast tissue was sequentially extracted using hexane, propanol, methanol and water as solvents and extracts were analyzed using reverse phase HPLC and C-13 NMR. Results indicated a large variety of aromatic constituents including flavonoids and hydroxy-methoxy cinnamic acids linked to oligosaccharides and hydroxy acids through glycosidic linkages. The extracts inhibited cellulase and pectinase activities and can thus influence retting.
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| 8. |
- Gorini, Giuseppe, et al.
(author)
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Neutron Emission from Beam-Injected Fast Tritons in JET Plasmas with Reversed or Monotonic Magnetic Shear.
- 2004
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In: 31st EPS Conference on Plasma Physics. ; , s. 4-
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Conference paper (other academic/artistic)abstract
- The neutron emission from fast tritons in plasmas with different magnetic shearconfigurations has been investigated in a dedicated experiment on JET. Short pulses ofneutral beam injection were used to deposit fast tritons in deuterium plasmas. By comparingthe measured neutron yield with predictions based on DT reaction calculations, fast tritonlosses can be assessed. The latter are expected to be very low according to neoclassicalpredictions based on Fokker-Planck simulation [1]. Much larger “anomalous” beam-ionlosses (up to 40%) have been reported in TFTR experiments for plasma conditions withreversed magnetic shear [2]. The TFTR experiments indicated an excess DT rate in thesimulation and, to a lesser extent, in the DD rate and plasma stored energy. This wasinterpreted as anomalous beam-ion loss associated with reverse shear due to an unidentifiedloss mechanism. Evidence of a similar effect was searched for in the JET experimentsreported in this paper.
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| 9. |
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| 10. |
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| 11. |
- Hedelin, R, et al.
(author)
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Heart rate variability in athletes : relationship with central and peripheral performance.
- 2001
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In: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 33:8, s. 1394-1398
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate relationships between heart rate variability (HRV) and peripheral and central performance measures, 17 cross-country (X-C) skiers and seven canoeists were studied before and after a training period of 7 months. METHODS: For the skiers and canoeists respectively, leg and arm peak torque (Tq), time to peak torque (TiTq), and total work (Wrk) were measured in an isokinetic dynamometer. Maximal oxygen uptakes (VO(2max)) were obtained from treadmill tests. Power spectral analysis of HRV was performed on electrocardiographic recordings in the resting supine position and after a tilt to yield power in the low-frequency (0.04--0.15 Hz) and high-frequency (0.15--0.45 Hz) components of HRV. RESULTS: The change in normalized LF-variability in standing (Delta LFnT) correlated (P < 0.01) with the changes in TiTq (r = 0.63), max lactate (r = -0.63), and VO(2max) (r = -0.53). The change in absolute LFT was inversely correlated with the change in Tq. Subjects who improved VO(2max) were characterized by consistently higher high-frequency and total HRV than subjects with deteriorated aerobic capacity (P < 0.05). CONCLUSION: The results suggest that improved measures of both peripheral and central (aerobic) work capacities were associated with a reduction of low-frequency HRV in the tilted position. High-frequency and total HRV did not change in proportion with changes in muscle performance or aerobic capacity, but the ability to further improve VO(2max) with training in these already fit subjects seemed to depend on their average levels of these HRV measures, interpreted to reflect parasympathetic activity.
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| 12. |
- Hedelin, R, et al.
(author)
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Pre- and post-season heart rate variability in adolescent cross-country skiers.
- 2000
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In: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 10:5, s. 298-303
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Journal article (peer-reviewed)abstract
- To investigate the effects on cardiac autonomic control after a competitive cross-country skiing season, 9 females and 8 males, 16-19 years old, performed tilt-table heart rate variability (HRV) recordings and incremental treadmill tests before (August), and after (April the following year) the most intensive period of training and competition. Spectral analysis of HRV showed increased total variability at rest and reduced low frequency variability in the tilted position (LFtilt) at the second test (P<0.05). The female subgroup showed consistently higher high frequency (HF) and total heart rate variability than males. Total run time (RunT) increased from 18.5+/-1.9 min to 19.4+/-1.7 min (mean+/-SD) in the entire group (P<0.05), while VO2max only showed a non-significant increase (0.05 <0.10). Submaximal heart rates (HRsubm) were reduced by an average of 4 beats (P<0.01) but maximal HR was unchanged. Performance data suggest a positive training effect. Following training, the increased total HRV the reduced LFtilt (both at rest), and the lower submaximal heart rates indicate an altered control of heart rate both at rest and during exercise. The consistently higher HF and total variability in the females indicate an increased parasympathetic activity in females compared with males.
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| 13. |
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| 14. |
- Henriksson, H., et al.
(author)
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N-linked glycosylation of native and recombinant cauliflower xyloglucan endotransglycosylase 16A
- 2003
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In: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 375, s. 61-73
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Journal article (peer-reviewed)abstract
- The gene encoding a XET (xyloglucan endotransglycosylase) from cauliflower (Brassica oleracea var. botrytis) florets has been cloned and sequenced. Sequence analysis indicated a high degree of similarity to other XET enzymes belonging to glycosyl hydrolase family 16 (GH16). In addition to the conserved GH16 catalytic sequence motif EIDFE, there exists one potential N-linked glycosylation site. which is also highly conserved in XET enzymes from this family. Purification of the corresponding protein from extracts of cauliflower florets allowed the fractionation of a single, pure glycoform. which was analysed by MS techniques. Accurate protein mass determination following the enzymic deglycosylation of this glycoform indicated the presence of a high-mannose-type glycan of the general structure GlcNAc(2)Man(6). LC/MS and MS/MS (tandem MS) analysis provided supporting evidence for this structure and confirmed that the glycosylation site (underlined) was situated close to the predicted catalytic residues in the conserved sequence YLSSTNNEHDEIDFEFLGNRTGQPVILQTNVFTGGK. Heterologous expression in Pichia pastoris produced a range of protein glycoforms, which were, on average, more highly mannosylated than the purified native enzyme. This difference in glycosylation did not influence the apparent enzymic activity of the enzyme significantly. However, the removal of high-mannose glycosylation in recombinant cauliflower XET by endoglycosidase H, quantified by electrospray-ionization MS, caused a 40 % decrease in the transglycosylation activity of the enzyme. No hydrolytic activity was detected in native or heterologously expressed BobXET16A, even when almost completely deglycosylated.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Johansson, M., et al.
(author)
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Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma
- 2000
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In: British Journal of Cancer. - : Cancer Research Campaign. - 0007-0920 .- 1532-1827. ; 83:6, s. 826-832
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Journal article (peer-reviewed)abstract
- Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma.
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| 20. |
- Kimmel, L. B., et al.
(author)
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Nontraditionally retted flax for dry cotton blend spinning
- 2001
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In: Textile research journal. - : SAGE Publications. - 0040-5175 .- 1746-7748. ; 71:5, s. 375-380
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Journal article (peer-reviewed)abstract
- Extracting flax fibers from the stems of Linum usitatissimum plants has traditionally been a costly, labor-intensive process, largely restricted to Europe and Asia. The naturally long, strong fibers are typically processed on wet spinning machines that are not available in the United States. However, the resurgent popularity of flax has promoted an interest in devising more economical methods of producing and processing the fibers domestically. This preliminary study investigates the use of flax fibers extracted by mechanical, chemical, and enzymatic retting as well as traditional (dew) retting methods. The experimental fibers show promise for spinning on common cotton machinery in blends with cotton. The research has produced a series of medium-count, experimental apparel-grade yarns with an attractive appearance and acceptable hand. With refinement, chemical or enzyme retting can perhaps become an ecologically sound and cost effective method of producing flax fibers.
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| 21. |
- Krook, A, et al.
(author)
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Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients
- 2000
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 49:2, s. 284-292
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Journal article (peer-reviewed)abstract
- We characterized metabolic and mitogenic signaling pathways in isolated skeletal muscle from well-matched type 2 diabetic and control subjects. Time course studies of the insulin receptor, insulin receptor substrate (IRS)-1/2, and phosphatidylinositol (PI) 3-kinase revealed that signal transduction through this pathway was engaged between 4 and 40 min. Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). Impaired glucose transport activity was noted at all insulin concentrations (0.6-60 nmol/l). Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. Impaired insulin signal transduction in skeletal muscle from type 2 diabetic patients may partly account for reduced insulin-stimulated glucose transport; however, additional defects are likely to play a role.
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| 22. |
- Larsson, Britt, et al.
(author)
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The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls
- 2000
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In: Pain. - 1872-6623 .- 0304-3959. ; 84:2-3, s. 379-387
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Journal article (peer-reviewed)abstract
- The association of cytochrome c oxidase negative fibres (COX-negative) and ragged-red fibres (RR-fibres) with work related trapezius myalgia has been proposed. Hitherto studies have been small or without control groups. The aim of the present study was to investigate the prevalences of RR-fibres and COX-negative fibres in female cleaners with (n=25) and without (n=23) trapezius myalgia and in clinically healthy female teachers (n=21). The cleaners did mainly floor cleaning requiring monotonous loading on the trapezius muscle. A questionnaire covering background data and aspects of pain (prevalence, duration, intensity and influence on daily living) was answered. Biopsies were obtained from the trapezius muscle by an open surgical technique. The three groups did not differ in prevalence of COX-negative or COX-superpositive (i.e. type-I fibres with extremely strong brownish reaction in both the COX and SDH/COX stainings) fibres. The prevalence of COX-negative fibres was age dependent. Two subgroups of RR-fibres were present when stained for COX; COX-negative (73%) and COX-superpositive (26%) fibres. Forty-two percent of the COX-negative fibres were RR-fibres and 79% of the COX-superpositive were RR-fibres. A significantly (P=0.002) higher proportion of the COX-superpositive fibres in the cleaners were RR-fibres compared to the teachers. Multivariate regression analysis revealed that age, occupation as cleaner and a tender point in the trapezius were significantly associated with increased prevalences of RR-fibres; a cleaner with a tender point had a 4.35 higher prevalence of RR-fibres compared to a teacher without a tender point. No correlations between other pain related variables and prevalence of RR-fibres were noted. In conclusion, RR-fibres but not COX-negative or COX-superpositive fibres were correlated with cleaning work tasks and with a tender point in the trapezius.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Linderholm, BK, et al.
(author)
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The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer
- 2001
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 61:5, s. 2256-2260
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Journal article (peer-reviewed)abstract
- Wild-type p53 protein has been shown to inhibit angiogenesis through thrombospondin in thepreclinical setting, Here, we determined the associations between the expression of the angiogenic factorvascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and types,in primary breast cancer. Cytosols from 224 primary breast cancer patients were analyzed with an enzyme immunoassay for determination of human VEGF(165) protein content. p53 status was determined hv cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC). and by a p53luminometric immunoassay (I,IA) method. Statistically significant associations was found between higher VEGF content and non-wild-type p53 status for all methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and the I,IA method (r = 0.427: P > 0.001), Highest VEGF values were detected in tumorswith p53 insertions, deletions, and stop codon mutations (P = 0.0043). Combining p53 status and VEGF content resulted in additional prognostic information, relapse-free survival (RFS: P = 0.0377), overall survival (OS; P = 0.0319), and breast cancer corrected survival (BCCS: P = 0.0292). In multivariate analysis, the relative hazard increased when the VEGF data were added to the p53 status, with a relative hazard of 1.7 for RFS and 3.0 for BCCS, compared with 1.1 fur RFS and 1.4 for BCCS among the patientswith either high VEGF content or p53 mutation. Higher VEGF content was statistically significantly correlated with a worse outcome fur patients with estrogen receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis withpoint estimates of 3.4 and 2.1 fur BCCS and RFS, respectively, VEGF expression is related to p53 statusin human breast cancer patients. Combining VEGF with p53 status resulted in better prognostic prediction.
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| 27. |
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| 28. |
- Lundgren-Eriksson, L., et al.
(author)
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Hypothermic modulation of doxorubicin, cisplatin and radiation cytotoxicity in vitro
- 2001
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In: Anticancer Res. - 0250-7005. ; 21:5, s. 3275-80
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Journal article (peer-reviewed)abstract
- BACKGROUND: The influence of hypothermia on doxorubicin, cisplatin and radiation cytotoxicity was investigated in vitro. MATERIALS AND METHODS: A human glioma cell line (251MG) in early exponential growth was exposed to doxorubicin or cisplatin at various concentrations for 4 hours, or X-irradiation at 28 degrees C or 37 degrees C. The cells continued growing in multi-well plates at 37 degrees C and were counted every third day until the end of the logarithmic phase, on day 13. RESULTS: Exposure to doxorubicin 0.05-0.5 microg/ml or cisplatin 1-10 microg/ml caused a dose-dependent inhibition of cell growth with a significantly reduced toxicity when exposed at 28 degrees C as compared to 37 degrees C. Irradiation with 4 Gy also resulted in less toxicity during hypothermia. Chlorpromazine 0.01-10 microg/ml, used to induce hypothermia in vivo (1), neither influenced, cellular growth itself nor interacted with doxorubicin, cisplatin or irradiation. CONCLUSION: Moderate hypothermia (28 degrees C) appears to protect against the cellular insult of doxorubicin, cisplatin and ionising irradiation and their consequences.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Raices, M., et al.
(author)
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Cellobiose quinone oxidoreductase from the white rot fungus Phanerochaete chrysosporium is produced by intracellular proteolysis of cellobiose dehydrogenase
- 2002
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In: Biochimica et Biophysica Acta, Gene Structure and Expression. - 0167-4781 .- 1879-2634. ; 1576:02-jan, s. 15-22
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Journal article (peer-reviewed)abstract
- The fungus Phanerochaete chrysosporium was grown in a 10-1 automatic fermenter using cellobiose us carbon source to monitor the induction of cellobiose dehydrogenase (CDH) and cellobiose quinone oxidoreductase (CBQ) enzymes, and to search for tentative cbq and cdh genes and their transcriptional products. After 24 h of induction, CDH was detected in the culture supernatant and a protein was recognized by a specific anti-CDH polyclonal antibody in the sonicated biomass. Northern blot experiments performed with several fungal RNA samples showed, after 24 h of induction. only one single species of an mRNA transcript corresponding in size to the cdh gene (2.5 kb) The relative amount of this transcript decreased as a function of time. Southern blot experiments done with genomic DNA and database search in the recently available genome information also ruled out the presence in this strain of a separate cbq gene distinct from the cdh gene, Taken together, these results demonstrated that CBQ originates from the cdh gene. Furthermore, it is not produced by differential splicing but by a posttranslational, predominantly intracellular, proteolytic cleavage,
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| 34. |
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| 35. |
- Sitnikov, R., et al.
(author)
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Nuclear magnetic resonance spectrometer with a frequency range extended below the megahertz region
- 2000
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In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 71:2, s. 450-457
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Journal article (peer-reviewed)abstract
- A conventional nuclear magnetic resonance (NMR) spectrometer with an original low-frequency limit of 2 MHz and equipped with an electromagnet is rebuilt to allow performing NMR experiments at resonance frequencies down to 100 kHz. The instrument is intended for accurate field-dependent spin relaxation studies. The preamplifier and the duplexer are completely replaced by new designs that provide low noise figure, large gain and fast recovery. The receiver, the transmitter, and the magnet power supply are modified to operate at low frequency (receiver and transmitter) and at low current (power supply). The performance of the instrument is demonstrated by H-2 NMR experiments in the 500 kHz-2 MHz region and is compared to that of instruments based on direct current-superconducting quantum interference device and operated on room-temperature samples.
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| 36. |
- Song, X M, et al.
(author)
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5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice.
- 2002
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In: Diabetologia. - 0012-186X .- 1432-0428. ; 45:1, s. 56-65
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.METHODS: Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days.RESULTS: Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal.CONCLUSION/INTERPRETATION: The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.
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| 37. |
- Stahlberg, J., et al.
(author)
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Structural basis for enantiomer binding and separation of a common beta-blocker : Crystal structure of cellobiohydrolase Cel7A with bound (S)-propranolol at 1.9 angstrom resolution
- 2001
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 305:1, s. 79-93
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Journal article (peer-reviewed)abstract
- Cellobiohydrolase Cel7A (previously called CBH 1), the major cellulase produced by the mould fungus Trichoderma reesei, has been successfully exploited as a chiral selector for separation of stereo-isomers of some important pharmaceutical compounds, e.g. adrenergic beta -blockers. Previous investigations, including experiments with catalytically deficient mutants of Cel7A, point unanimously to the active site as being responsible for discrimination of enantiomers. In this work the structural basis for enantioselectivity of basic drugs by Cel7A has been studied by X-ray crystallography. The catalytic domain of Cel7A was co-crystallised with the (S)-enantiomer of a common beta -blocker, propranolol, at pH 7, and the structure of the complex was determined and refined at 1.9 Angstrom resolution. Indeed, (S)-propranolol binds at the active site, in glucosyl-binding subsites -1/ + 1. The catalytic residues Glu212 and Glu217 make tight salt links with the secondary amino group of (S)-propranolol. The oxygen atom attached to the chiral centre of (S)-propranolol forms hydrogen bonds to the nucleophile Glu212 O-epsilon1 and to Gln175 N-epsilon2, whereas the aromatic naphthyl moiety stacks with the indole ring of Trp376 in site +1. The bidentate charge interaction with the catalytic glutamate residues is apparently crucial, since no enantioselectivity has been obtained with the catalytically deficient mutants E212Q and E217Q. Activity inhibition experiments with wild-type Cel7A were performed in conditions close to those used for crystallisation. Competitive inhibition constants for (R)- and (S)-propranolol were determined at 220 muM and 44 muM, respectively, corresponding to binding free energies of 20 kJ/ mol and 24 kJ/mol, respectively. The K-i value for (R)-propranolol was 57-fold lower than the highest concentration, 12.5 mM, used in co-crystallisation experiments. Still several attempts to obtain a complex with the (R)-enantiomer have failed. By using cellobiose as a selective competing ligand, the retention of the enantiomers of propranolol on the chiral stationary phase (CSP) based on Cel7A mutant D214N were resolved into enantioselective and non-selective binding. The enantioselective binding was weaker for both enantiomers on D214N-CSP than on wild-type-CSP.
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| 38. |
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| 39. |
- Tornblom, M., et al.
(author)
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A H-2 NMR study of order and dynamics in the cubic I-1 phase of the dodecyltrimethylammonium chloride/water system
- 2000
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In: Liquid crystals (Print). - 0267-8292 .- 1366-5855. ; 27:7, s. 943-955
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Journal article (peer-reviewed)abstract
- The micellar cubic phase I-1 of the dodecyltrimethylammonium chloride (C(12)TACl)/water system has been studied by H-2 NMR spectroscopy. Relaxation rates of selectively deuteriated surfactant were measured at several frequencies down to 0.5 MHz in the temperature range 25-61 degrees C. The results are interpreted within models for the reorientational dynamics in I, phases and it is concluded that the remaining order after surface diffusion and aggregate rotation is small and does not vary substantially with temperature. The results are discussed in relation to the two prevailing models for the structure of these phases as suggested (separately) by Fontell and Vargas. At 0 degrees C the 2H NMR Spectrum from perdeuteriated n-dodecane solubilized in this phase shows static quadrupole splittings with a magnitude that is in good agreement with the results obtained from the analysis of the relaxation data.
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| 40. |
- Tornblom, M., et al.
(author)
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Field-dependent NMR relaxation study of aggregation and dynamics in dilute to concentrated micellar decylammonium chloride solutions
- 2000
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1089-5647 .- 1520-6106 .- 1520-5207. ; 104:7, s. 1529-1538
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Journal article (peer-reviewed)abstract
- The surfactant aggregation behavior in aqueous decylammonium chloride solutions for concentrations between 5 and 29 wt % was studied by H-2 nuclear magnetic relaxation dispersion in the 0.5-77-MHz frequency range. Below the second cmc the micelles can be described as polydisperse fairly small aggregates undergoing unhindered Brownian rotation. Above the second cme the micelles are rod shaped and grow with increasing concentration, and as a consequence the tumbling of the micelles eventually becomes restricted by neighboring aggregates, which is demonstrated by the low-frequency relaxation data. The restricted reorientation of the micelles in the concentrated solution has been modeled as rotational diffusion in a hard-walled double cone potential of mean torque.
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| 41. |
- Tsuchida, Hiroki, et al.
(author)
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Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects.
- 2002
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In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 445:1, s. 25-31
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Journal article (peer-reviewed)abstract
- The gene of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85alpha splice variants may be altered in skeletal muscle from subjects with type 2 diabetes mellitus. Skeletal muscle biopsies were obtained from nine type 2 diabetic and eight healthy men, matched for age, body mass index (BMI) and physical fitness. PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85alpha mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects ( P<0.05). p85alpha mRNA abundance was positively correlated with plasma insulin concentration ( P<0.01) and serum glucose concentration ( P<0.01). Despite this, protein levels of p85alpha, p55alpha, and the novel human p50alpha were not altered in type 2 diabetic subjects. Thus, although gene expression of full-length p85alpha is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein levels. Therefore, defects in PI 3-kinase activity are likely due to impaired activation of the enzyme rather than changes in protein expression of the isoforms of the regulatory subunit.
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| 42. |
- Wahren, J, et al.
(author)
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Role of C-peptide in human physiology
- 2000
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In: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 278:5, s. E759-E768
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Journal article (peer-reviewed)
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| 43. |
- Yu, M, et al.
(author)
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Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport.
- 2001
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 90:1, s. 29-34
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Journal article (peer-reviewed)abstract
- Vastus lateralis muscle biopsies were obtained from endurance-trained (running approximately 50 km/wk) and untrained (no regular physical exercise) men, and the expression of an array of insulin-signaling intermediates was determined. Expression of insulin receptor and insulin receptor substrate-1 and -2 was decreased 44% (P < 0.05), 57% (P < 0.001), and 77% (P < 0.001), respectively, in trained vs. untrained muscle. The downstream signaling target, Akt kinase, was not altered in trained subjects. Components of the mitogenic signaling cascade were also assessed. Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase expression was 190% greater (P < 0.05), whereas p38 mitogen-activated protein kinase expression was 32% lower (P < 0.05), in trained vs. untrained muscle. GLUT-4 protein expression was twofold higher (P < 0.05), and the GLUT-4 vesicle-associated protein, the insulin-regulated aminopeptidase, was increased 4.7-fold (P < 0. 05) in trained muscle. In conclusion, the expression of proteins involved in signal transduction is altered in skeletal muscle from well-trained athletes. Downregulation of early components of the insulin-signaling cascade may occur in response to increased insulin sensitivity associated with endurance training.
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| 44. |
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