| 1. |
- Lehmann, O. J., et al.
(författare)
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Novel anterior segment phenotypes resulting from forkhead gene alterations: Evidence for cross-species conservation of function
- 2003
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:6, s. 2627-2633
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Mutations in murine and human Versions of an ancestrally related gene usually result in similar phenotypes. However, interspecics differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS. A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS. Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.
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| 2. |
- Capala, J, et al.
(författare)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Carlsson, T., et al.
(författare)
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HCV RNA levels during therapy with amantadine in addition to interferonand ribavirin in chronic hepatitis C patients with previous nonresponse orresponse/relapse to interferon and ribavirin
- 2000
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 7:6, s. 409-413
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Tidskriftsartikel (refereegranskat)abstract
- Interferon (IFN) alpha in combination with ribavirin (RIB) is standard therapy for patients with chronic hepatitis C virus (HCV) infection. However, many patients do not respond with sustained HCV clearance to this therapy. At present, no accepted treatment strategy exists for these patients. Recent preliminary data have suggested that amantadine (AMA) is effective against HCV infection. In a pilot study, we treated 13 nonresponders and 10 response/ relapsers to previous IFN/RIB therapy with AMA 200 mg per day in combination with IFN 3 MU thrice weekly, and RIB 1000 mg per day for 24 weeks, with a 24-week follow-up period after end-of-treatment. At the end-of-treatment, 1 previous nonresponder and 5 previous response/relapsers were HCV RNA negative. At the end of follow-up, only 1 previous response/relapser remained HCV RNA negative and had a sustained response. During therapy, serum HCV RNA became undetectable in 4 previous nonresponders, of whom 3 had a breakthrough at week 24. Twenty-one patients continued therapy without dose reductions. One patient discontinued therapy prematurely due to sleeping disturbances, and another patient was withdrawn from therapy due to heavy alcohol intake. We conclude that the addition of AMA to IFN and RIB was well tolerated but had little, if any, impact on HCV RNA eradication in nonresponders or response/relapsers to previous IFN/RIB combination therapy.
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| 4. |
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| 5. |
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| 6. |
- Abrahamsson, Kajsa H., 1956, et al.
(författare)
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Ambivalence in Coping with Dental Fear and Avoidance: A Qualitative Study
- 2002
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Ingår i: Journal of Health Psychology. - : SAGE Publications. - 1359-1053 .- 1461-7277. ; 7:6, s. 653-664
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Tidskriftsartikel (refereegranskat)abstract
- Dental phobia is a widespread problem, which can have significant impact on the individual's health and daily life. This grounded theory study aims to explore the situation of dental phobic patients: how dental phobia interferes with their normal routines and functioning, social activities and relationships, what factors contribute to the maintenance of dental fear and how they cope with their fear. In the qualitative analysis of thematized in-depth interviews four main categories were developed: threat to self-respect and well-being, avoidance, readiness to act and ambivalence in coping. The results show that several psychological and social factors interact in determining how dental phobic individuals cope with their fear, and demonstrate in what way dental fear affects their daily lives.
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| 7. |
- Abrahamsson, Kajsa H., 1956, et al.
(författare)
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Dental phobic patients' view of dental anxiety and experiences in dental care: a qualitative study.
- 2002
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Ingår i: Scandinavian journal of caring sciences. - 0283-9318. ; 16:2, s. 188-96
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Tidskriftsartikel (refereegranskat)abstract
- Dental phobic patients' view of dental anxiety and experiences in dental care: a qualitative study The aim of this study was to explore and describe dental phobic patients' perceptions of their dental fear and experiences in dental care. The study sample consisted of 18 participants (12 women), with a mean age of 39.4 years, selected consecutively from patients applying for treatment at a specialized dental fear clinic in G?teborg, Sweden. Dental fear, assessed by the Dental Anxiety Scale, showed score levels well over established levels for severe dental fear. The method for sampling and analysis was inspired by the constant comparative method for Grounded Theory (GT). The thematized in-depth interviews took place outside the clinic and lasted for 1-1.5 h. All the interviews were conducted by the first author (KHA), audiotaped and transcribed verbatim. Three higher-order categories were developed and labelled existential threat, vulnerability and unsupportive dentist. Existential threat was identified as the core category, describing the central meaning of the subjects' experiences in dental care. The core category included two dimensions, labelled threat of violation and threat of loss of autonomy and independence. The core category and the descriptive categories are integrated in a model framing the process of dental fear, as described by the informants. In conclusion, the onset of dental fear was commonly related to individual vulnerability and to traumatic dental care experiences, where perceived negative dentist behaviour played a significant role. The patient was caught in a 'vicious circle' that was difficult to break, and where fear and anxiety were maintained by negative expectations about treatment and about patient's own ability to cope in dental care situations.
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| 8. |
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| 9. |
- Andersson, R. M., et al.
(författare)
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Characterization of probe binding and comparison of its influence on fluorescence lifetime of two pH-sensitive benzo c xanthene dyes using intensity-modulated multiple-wavelength scanning technique
- 2000
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 283:1, s. 104-110
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative pH imaging using the carboxy semi-naphthofluorescein dyes SNAFL-1 and SNAFL-2 can be performed by measurement of intensity ratios or fluorescence lifetimes. However, there is a controversy as to whether the latter method has the practical advantage of a straightforward pH calibration in buffers compared to a cumbersome and time-consuming procedure in cells. In this study we have undertaken a systematic study of the potential factors influencing the fluorescence lifetime of the probes at different pH using confocal microscopy. In vitro results demonstrate that factors such as lipid and protein concentrations have a substantial influence on pH measurements based on fluorescence lifetime. The pH could be overestimated by more than 2 pH units. Studies in permeabilized COS-7 cells demonstrate the same trends as observed in the in vitro studies.
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| 10. |
- Angulo Barrios, C., et al.
(författare)
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GaAs/AlGaAs buried-heterostructure laser diodes with semi-insulating GaInP:Fe regrowth
- 2001
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Ingår i: Lasers and Electro-Optics, 2001. CLEO/Pacific Rim 2001. The 4th Pacific Rim Conference on.
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Konferensbidrag (refereegranskat)abstract
- GaAs/AlGaAs buried-heterostructure in-plane lasers and vertical-cavity surface-emitting lasers using GaInP:Fe as the burying layer have been fabricated and investigated. Regrowth of GaInP:Fe around etched laser mesas was achieved by hydride vapor phase epitaxy. The lasers exhibit good performance under CW operation and show promising high-speed characteristics.
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| 11. |
- Aranburu, A., et al.
(författare)
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Transcription factor AP-4 is a ligand for immunoglobulin-κ promoter E-box elements
- 2001
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Ingår i: Biochemical Journal. - 0264-6021. ; 354:2, s. 431-438
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin (Ig)-κ promoters from humans and mice share conserved sequences. The octamer element is common to all Ig promoters and pivotal for their function. However, other conserved sequence motifs, that differ between lg variable gene families, are required for normal promoter function. These conserved motifs do not stimulate transcription in the absence of an octamer. One example is an E-box of the E47/E12 type (5′-CAGCTG-3′), which is found in all promoters of the human and murine Ig-κ gene subgroups/families, with the exception of subgroups II and VI and their related murine families. In the present study we show that the ubiquitously expressed transcription factor AP-4, and not E47, interacts specifically with the κ promoter E-boxes when tested in electrophoretic mobility-shift assays using nuclear extracts derived from human and murine B-cell lines. Furthermore, AP-4, unlike E47, did not act as a transactivator, which is in agreement with previous studies on intact κ promoters, showing that transcription is absent when the octamer element has been mutated. Based on these data, and the conservation of the 5′-CAGCTG-3′ motif among human and murine κ promoters, we propose that AP-4 is the major ligand for Ig-κ promoter E-boxes.
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| 12. |
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| 13. |
- Barrios, C. A., et al.
(författare)
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GaAs/AlGaAs buried-heterostructure vertical-cavity surface-emitting laser with semi-insulating GalnP : Fe regrowth
- 2000
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Ingår i: Electronics Letters. - 0013-5194 .- 1350-911X. ; 36:18, s. 1542-1544
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the first results of a GaAs/AlGaAs buried-heterostructure vertical-cavity surface-emitting laser (VCSEL) with semi-insulating Ga0.51In0.49P:Fe (SI-GaInP:Fe) as the burying layer. Regrowth of SI-GaInP:Fe around 15 mu m diameter and 8 mu m tall VCSEL mesas was carried out by hydride vapour phase epitaxy (HVPE). Under room temperature continuous wave (CW) operation. the device exhibited a threshold current of 3.5mA, a differential quantum efficency of 33% and a light output power of 4.2mW. CW operation at temperatures up to 97 degrees C is also demonstrated.
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| 14. |
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| 15. |
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| 16. |
- Bolling-Sternevald, Elisabeth, et al.
(författare)
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Effect of Profound Acid Suppression in Functional Dyspepsia : a Double-Blind, Randomized, Placebo-Controlled Trial
- 2002
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 37:12, s. 1395-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment.Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards.Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy.Conclusion: A subset of patients with FD will respond to therapy with omeprazole.
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| 17. |
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| 18. |
- Bolling-Sternevald, Elisabeth, et al.
(författare)
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Self-administered symptom questionnaires in patients with dyspepsia and their yield in discriminating between endoscopic diagnoses
- 2002
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Ingår i: Digestive diseases. - : S. Karger AG. - 0257-2753 .- 1421-9875. ; 20:2, s. 191-198
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Symptoms are generally considered to be poor predictors of organic findings in patients with dyspepsia. We aimed at evaluating whether specific gastrointestinal symptoms, identified by self-administered questionnaires, correlate with specific endoscopic diagnoses and discriminate organic from functional dyspepsia. METHODS: Adult patients with pain or discomfort centred in the upper abdominal region were consecutively enrolled. Patients with heartburn, acid regurgitation, or defaecation and bowel habit problems as their predominant symptoms were excluded. Three self-administered questionnaires were applied before an oesophagogastroduodenoscopy was performed. RESULTS: Among the 799 patients, 50.6% had a normal endoscopy. Endoscopic diagnoses comprised: non-erosive oesophagitis (7.5%), erosive oesophagitis (11.1%), Barrett's oesophagus (1.1%), gastritis/duodenitis (8.4%), gastric ulcer (4.5%), duodenal ulcer (8.3%), and cancer (1.3%). Non-dominant heartburn and acid regurgitation were significantly more common in patients with organic dyspepsia, whereas hunger pains and rumbling occurred more often in those with functional dyspepsia. Multivariate analyses demonstrated that younger age, female gender, high scores for hunger pain, rumbling, hard stools, low scores for heartburn, and acid regurgitation predicted functional dyspepsia. CONCLUSIONS: Self-administered questionnaires revealed differences in the symptom patterns between patients with functional and organic dyspepsia. Furthermore, the health-related well-being in patients with functional and organic dyspepsia centred was impaired to the same extent.
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| 19. |
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| 20. |
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| 21. |
- Carlsson, C., et al.
(författare)
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Performance characteristics of buried heterostructure VCSELs using semi-insulating GaInP : Fe regrowth
- 2001
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Ingår i: IEEE Journal of Quantum Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9197 .- 1558-1713. ; 37:7, s. 945-950
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Tidskriftsartikel (refereegranskat)abstract
- We have fabricated GaAs-AlGaAs buried heterostructure vertical cavity surface emitting lasers, emitting at 850 nm, using semi-insulating GaInP:Fe regrowth and investigated their static properties. Lasers of different size (10-21 mum) have threshold currents in the range 2.8-7.0 mA, and produce a maximum output power of 1.7-6.0 mW at room temperature. The variation of threshold current with device size shows that the leakage current at the regrowth interface accounts for a significant part of the injection current. In spite of this, a differential quantum efficiency in the range 20%-30% is obtained which indicates that the regrowth interface is smooth and does not introduce any significant scattering loss. Studies of the transverse mode properties suggest that the GaInP provides weak guiding, resulting in single mode operation up to an output power of 0.7 mW and a beam divergence of only 6 degrees for lasers as large as 10 mum.
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| 22. |
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| 23. |
- Carlsson, Kjell, et al.
(författare)
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Confocal pH imaging of microscopic specimens using fluorescence lifetimes and phase fluorometry : influence of parameter choice on system performance
- 2000
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 199, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the performance of confocal pH imaging when using phase fluorometry and fluorophores with pH-dependent lifetimes. In these experiments, the specimen is illuminated by a laser beam, whose intensity is sinusoidally modulated. The lifetime-dependent phase shift in the fluorescent signal is detected by a lock-in amplifier, and converted into a pH value through a calibration procedure. A theoretical investigation is made of how the different system parameters will influence the results concerning sensitivity and noise. Experiments carried out with the fluorophore SNAFL-2 support these theoretical predictions. It is found that, under realistic experimental conditions, we can expect a pH change of 0.1 units to be easily detected in an 8-bit digital image. However, the pixel-to-pixel root mean square noise is often of the order of one pH unit. This comparatively high level of noise has its origin in photon quantum noise. pH measurements on living cells show a systematic deviation from expected values. This discrepancy appears to be the result of fluorophore interaction with various cell constituents, and is the subject of further investigation.
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| 24. |
- Carlsson, Lena, et al.
(författare)
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Differences in the distribution of synemin, paranemin, and plectin in skeletal muscles of wild-type and desmin knock-out mice
- 2000
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Ingår i: Histochemistry and Cell Biology. - : Springer. - 0948-6143 .- 1432-119X. ; 114:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- Mice lacking the gene encoding for the intermediate filament protein desmin have a surprisingly normal myofibrillar organization in skeletal muscle fibers, although myopathy develops in highly used muscles. In the present study we examined how synemin, paranemin, and plectin, three key cytoskeletal proteins related to desmin, are organized in normal and desmin knock-out (K/O) mice. We show that in wild-type mice, synemin, paranemin, and plectin were colocalized with desmin in Z-disc-associated striations and at the sarcolemma. All three proteins were also present at the myotendinous junctions and in the postsynaptic area of motor endplates. In the desmin K/O mice the distribution of plectin was unaffected, whereas synemin and paranemin were partly affected. The Z-disc-associated striations were in general no longer present in between the myofibrils. In contrast, at the myotendinous and neuromuscular junctions synemin and paranemin were still present. Our study shows that plectin differs from synemin and paranemin in its binding properties to the myofibrillar Z-discs and that the cytoskeleton in junctional areas is particularly complex in its organization.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Greiner, R., et al.
(författare)
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Pathway of dephosphorylation of myo-inositol hexakisphosphate by phytases of legume seeds
- 2002
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 50:23, s. 6865-6870
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Tidskriftsartikel (refereegranskat)abstract
- Using a combination of high-performance ion chromatography analysis and kinetic studies, the pathway of dephosphorylation of myo-inositol hexakisphosphate by the phytases purified from faba bean and lupine seeds, respectively, was established. The data demonstrate that the legume seed phytases under investigation dephosphorylate myo-inositol hexakisphosphate in a stereospecific way. The phytase from faba bean seeds and the phytase LP2 from lupine seeds degrade phytate by sequential removal of phosphate groups via D-Ins(1,2,3,5,6)P5, D-Ins(1,2,5,6)P4, D-Ins(1,2,6)P3, and D-Ins(1,2)P2 to finally Ins(2)P, whereas the phytases LP11 and LP12 from lupine seeds generate the final degradation product Ins(2)P via D-Ins(1,2,4,5,6)P5, D-Ins(1,2,5,6)P4, D-Ins(1,2,6)P3, and D-Ins(1,2)P2.
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| 33. |
- Greiner, R., et al.
(författare)
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Stereospecificity of myo-inositol hexakisphosphate dephosphorylation by a phytate-degrading enzyme of baker's yeast
- 2001
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 49:5, s. 2228-2233
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Tidskriftsartikel (refereegranskat)abstract
- During food processing such as baking, phytate is dephosphorylated to produce degradation products, such as myo-inositol pentakis-, tetrakis-, tris-, bis-, and monophosphates. Certain myo-inositol phosphates have been proposed to have positive effects on human health. The position of the phosphate groups on the myo-inositol ring is thereby of great significance for their physiological functions. Using a combination of high-performance ion chromatography analysis and kinetic studies the stereospecificity of myo-inositol hexakisphosphate dephosphorylation by a phytate-degrading enzyme from baker's yeast (Saccharomyces cerevisiae) was established. The data demonstrate that the phytate-degrading enzyme from baker's yeast dephosphorylates myo-inositol hexakisphosphate in a stereospecific way by sequential removal of phosphate groups via D-Ins(1,2,4,5,6)P5, D-Ins(1,2,5,6)P4, D-Ins(1,2,6)P3, D-Ins(1,2)P2, to finally Ins(2)P (notation 3/4/5/6/1). Knowledge of the absolute stereochemical specificity of the baker's yeast phytase allows use of the enzyme to produce defined myo-inositol phosphates for kinetic and physiological studies.
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| 34. |
- Greiner, R., et al.
(författare)
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Stereospecificity of myo-inositol hexakisphosphate dephosphorylation by a phytate-degrading enzyme of Escherichia coli
- 2000
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Ingår i: Journal of Biotechnology. - 0168-1656 .- 1873-4863. ; 84:1, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- Using a combination of high-performance ion chromatography analysis and kinetic studies, the stereospecificity of myo-inositol hexakisphosphate dephosphorylation by the phytate-degrading enzyme P2 of Escherichia coli was established. High-performance ion chromatography revealed that the phytate- degrading enzyme P2 of E. coli degrades myo-inositol hexakisphosphate by stepwise dephosphorylation via D/L-Ins(1,2,3,4,5)P5, D/L-Ins(2,3,4,5)P4, D/L-Ins(2,4,5)P3 or D/L-Ins(1,2,4)P3, D/L-Ins(1,2)P2 or Ins(2,5)P2 or D/L-Ins(4,5)P2 to finally Ins(2)P or Ins(5)P. Kinetic parameters for myo- inositol pentakisphosphate hydrolysis by E. coli and wheat phytase, respectively, showed that the myo-inositol pentakisphosphate intermediate produced either by the phytate-degrading enzyme of wheat or E. coli are not identical. The absolute configuration of the myo-inositol pentakisphosphate isomer produced by the E. coli enzyme was determined by taking into consideration that wheat phytase produces predominantly the D- Ins(1,2,3,5,6)P5 isomer (Lim, P.E., Tate, M.E., 1973. The phytases: II. Properties of phytase fraction F1 and F2 from wheat bran and the myo- inositol phosphates produced by fraction F2. Biochim. Biophys. Acta 302, 326-328). The data demonstrate that the phytate-degrading enzyme P2 of E. coli dephosphorylates myo-inositol hexakisphosphate in a stereospecific way by sequential removal of phosphate groups via D-Ins(1,2,3,4,5)P5, D- Ins(2,3,4,5)P4, D-Ins(2,4,5)P3, Ins(2,5)P2 to finally Ins(2)P (notation 6/1/3/4/5). (C) 2000 Elsevier Science B.V.Using a combination of high-performance ion chromatography analysis and kinetic studies, the stereospecificity of myo-inositol hexakisphosphate dephosphorylation by the phytate-degrading enzyme P2 of Escherichia coli was established. High-performance ion chromatography revealed that the phytate-degrading enzyme P2 of E. coli degrades myo-inositol hexakisphosphate by stepwise dephosphorylation via D/L-Ins(1,2,3,4,5)P5, D/L-Ins(2,3,4,5)P4, D/L-Ins(2,4,5)P3 or D/L-Ins(1,2,4)P3, D/L-Ins(1,2)P2 or Ins(2,5)P2 or D/L-Ins(4,5)P2 to finally Ins(2)P or Ins(5)P. Kinetic parameters for myo-inositol pentakisphosphate hydrolysis by E. coli and wheat phytase, respectively, showed that the myo-inositol pentakisphosphate intermediate produced either by the phytate-degrading enzyme of wheat or E. coli are not identical. The absolute configuration of the myo-inositol pentakisphosphate isomer produced by the E. coli enzyme was determined by taking into consideration that wheat phytase produces predominantly the D-Ins(1,2,3,5,6)P5 isomer. The data demonstrate that the phytate-degrading enzyme P2 of E. coli dephosphorylates myo-inositol hexakisphosphate in a stereospecific way by sequential removal of phosphate groups via D-Ins(1,2,3,4,5)P5, D-Ins(2,3,4,5)P4, D-Ins(2,4,5)P3, Ins(2,5)P2 to finally Ins(2)P (notation 6/1/3/4/5).
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| 35. |
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| 36. |
- Hamaguchi, I, et al.
(författare)
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Lentivirus vector gene expression during ES cell-derived hematopoietic development in vitro
- 2000
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 74:22, s. 84-10778
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Tidskriftsartikel (refereegranskat)abstract
- The murine embryonal stem (ES) cell virus (MESV) can express transgenes from the long terminal repeat (LTR) promoter/enhancer in undifferentiated ES cells, but expression is turned off upon differentiation to embryoid bodies (EBs) and hematopoietic cells in vitro. We examined whether a human immunodeficiency virus type 1-based lentivirus vector pseudotyped with the vesicular stomatitis virus G protein (VSV-G) could transduce ES cells efficiently and express the green fluorescent protein (GFP) transgene from an internal phosphoglycerate kinase (PGK) promoter throughout development to hematopoietic cells in vitro. An oncoretrovirus vector containing the MESV LTR and the GFP gene was used for comparison. Fluorescence-activated cell sorting analysis of transduced CCE ES cells showed 99.8 and 86.7% GPF-expressing ES cells in the VSV-G-pseudotyped lentivirus (multiplicity of infection [MOI] = 59)- and oncoretrovirus (MOI = 590)-transduced cells, respectively. Therefore, VSV-G pseudotyping of lentiviral and oncoretrovirus vectors leads to efficient transduction of ES cells. Lentivirus vector integration was verified in the ES cell colonies by Southern blot analysis. When the transduced ES cells were differentiated in vitro, expression from the oncoretrovirus LTR was severely reduced or extinct in day 6 EBs and ES cell-derived hematopoietic colonies. In contrast, many lentivirus-transduced colonies, expressing the GFP gene in the undifferentiated state, continued to express the transgene throughout in vitro development to EBs at day 6, and many continued to express in cells derived from hematopoietic colonies. This experimental system can be used to analyze lentivirus vector design for optimal expression in hematopoietic cells and for gain-of-function experiments during ES cell development in vitro.
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| 37. |
- Hellström, Christina, et al.
(författare)
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Psykologiska och sociala aspekter på kronisk smärta
- 2000
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Ingår i: Delaktig eller utanför. Sven G Carlsson, Erland Hjelmquist & Ingvar Lundberg, red.. - Umeå : Boréa. ; , s. 85-104
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Johansson, Thorsten, 1956-, et al.
(författare)
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Heidegger, Rorty and the Sublime
- 2001
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Ingår i: Omnium-gatherum. - Uppsala : Univ.. - 9150614533
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 39. |
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| 40. |
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| 41. |
- Knudsen, J.F., et al.
(författare)
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The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II
- 2004
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 28:5, s. 285-290
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Tidskriftsartikel (refereegranskat)abstract
- Cyclooxygenase-2 (COX-2) is up-regulated in stromal and inflammatory cells. The inducible COX-2 isoform is expressed during inflammation, in some cancers, and in brain tissue after global and focal ischemia. Tissue acidosis is a dominant factor in inflammation, and contributes to pain and hyperalgesia. Recently, compelling epidemiological and clinical evidence has documented the COX-independent effects of some COX-2 inhibitors (i.e., celecoxib, valdecoxib, and rofecoxib), among these effects are carbonic anhydrase (CA) inhibition. Carbonic anhydrases are zinc metalloenzymes expressed in various cell types, including those of the kidney, where they act as general acid-base catalysts. The kidneys are also known to express the highest concentration of COX-2 messenger ribonucleic acid. Celecoxib, like the prototypic CA inhibitor acetazolamide, is structurally characterized by an unsubstituted sulfonamide moiety. In the present study, we report that celecoxib exhibits the characteristics of a potent CA inhibitor, showing inhibitory human carbonic anhydrase II (hCAII) activity in the nanomolar range. Valdecoxib was relatively less potent. Rofecoxib, which lacks the unsubstituted sulfonamide moiety characteristic of CA inhibitors, showed no significant hCAII inhibitory activity. The current study corroborates our earlier report of structure-activity relationships as predictors of such metabolic events as hyperchloremia, acidosis, and changes in calcium and phosphate disposition, and clinical manifestations associated with CA inhibition reported with celecoxib. These data showing inhibition of hCAII by the unsubstituted sulfonamides celecoxib and valdecoxib, but not by rofecoxib, may have important implications for the elucidation of the mechanisms of action as well as the side effects associated with COX-2 inhibitors. © 2004 Springer Science+Business Media, Inc.
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| 42. |
- Kunz, S, et al.
(författare)
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Identification of a novel glucocorticoid receptor mutation in budesonide-resistant human bronchial epithelial cells
- 2003
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 17:12, s. 2566-2582
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Tidskriftsartikel (refereegranskat)abstract
- We developed a molecular genetic model to investigate glucocorticoid receptor (GR) signaling in human bronchial epithelial cells in response to the therapeutic steroid budesonide. Based on a genetic selection scheme using the human Chago K1 cell line and integrated copies of a glucocorticoid-responsive herpes simplex virus thymidine kinase gene and a green fluorescent protein gene, we isolated five Chago K1 variants that grew in media containing budesonide and ganciclovir. Three spontaneous budesonide-resistant subclones were found to express low levels of GR, whereas two mutants isolated from ethylmethane sulfonate-treated cultures contained normal levels of GR protein. Analysis of the GR coding sequence in the budesonide-resistant subclone Ch-BdE5 identified a novel Val to Met mutation at amino acid position 575 (GRV575M) which caused an 80% decrease in transcriptional regulatory functions with only a minimal effect on ligand binding activity. Homology modeling of the GR structure in this region of the hormone binding domain and molecular dynamic simulations suggested that the GRV575M mutation would have a decreased affinity for the LXXLL motif of p160 coactivators. To test this prediction, we performed transactivation and glutathione-S-transferase pull-down assays using the p160 coactivator glucocorticoid interacting protein 1 (GRIP1)/transcriptional intermediary factor 2 and found that GRV575M transcriptional activity was not enhanced by GRIP1 in transfected cells nor was it able to bind GRIP1 in vitro. Identification of the novel GRV575M variant in human bronchial epithelial cells using a molecular genetic selection scheme suggests that functional assays performed in relevant cell types could identify subtle defects in GR signaling that contribute to reduced steroid sensitivities in vivo.
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| 43. |
- Lubenow, Norbert, et al.
(författare)
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Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia. Report of four cases and review of literature.
- 2000
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 100:3, s. 115-25
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Tidskriftsartikel (refereegranskat)abstract
- Differential diagnosis between post-transfusion purpura (PTP) and heparin-induced thrombocytopenia (HIT) can be difficult in the initial stages of thrombocytopenia, as the early clinical presentations are often similar. Four patients are described who were suspected clinically of suffering from HIT. All four patients had recent blood transfusions and platelet alloantibodies, thus the diagnosis of PTP was made. One lethal gastrointestinal and one retroperitoneal hemorrhage developed in two of the four patients. Unusually, one patient was male and two different platelet alloantibodies were present in his serum; in another patient platelet alloantibodies and HIT-antibodies were detectable. To arrive at the right diagnosis as quickly as possible is vitally important since treatment, which has to be initiated promptly, is very different for the two syndromes. Thus, we suggest that in patients where HIT is suspected, additional information should be sought. If features consistent with PTP (such as a recent blood transfusion or a marked drop in platelet count to below 15 Gpt/L) are present, we recommend parallel testing for platelet alloantibodies to rule out PTP.
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| 44. |
- Lundmark, Richard, et al.
(författare)
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Regulated membrane recruitment of dynamin-2 mediated by sorting nexin 9.
- 2004
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 279:41, s. 42694-42702
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Tidskriftsartikel (refereegranskat)abstract
- The endocytic proteins sorting nexin 9 (SNX9) and dynamin-2 (Dyn2) assemble in the cytosol as a resting complex, together with a 41-kDa protein. We show here that the complex can be activated for membrane binding of SNX9 and Dyn2 by incubation of cytosol in the presence of ATP. SNX9 was essential for Dyn2 recruitment, whereas the reverse was not the case. RNA interference experiments confirmed that SNX9 functions as a mediator of Dyn2 recruitment to membranes in cells. The 41-kDa component was identified as the glycolytic enzyme aldolase. Aldolase bound with high affinity to a tryptophan-containing acidic sequence in SNX9 located close to its Phox homology domain, thereby blocking the membrane binding activity of SNX9. Phosphorylation of SNX9 released aldolase from the native cytosolic complex and rendered SNX9 competent for membrane binding. The results suggest that SNX9-dependent recruitment of Dyn2 to the membrane is regulated by an interaction between SNX9 and aldolase.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Panosso, R, et al.
(författare)
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Effect of grazing by a neotropical copepod, Notodiaptomus, on a natural cyanobacterial assemblage and on toxic and non-toxic cyanobacterial strains
- 2003
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Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 25:9, s. 1169-1175
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Tidskriftsartikel (refereegranskat)abstract
- The neotropical, freshwater copepod Notodiaptomus iheringi decreased the growth of small colonies in cyanobacteria-dominated plankton, indicating that they can be efficiently ingested and that they may represent an important food source for this copepod in reservoirs dominated by cyanobacteria. Cultured, colonial, toxic Microcystis aeruginosa was not affected, indicating that toxicity may cause a decrease in its ingestion by N. iheringi.
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