Biomedical subjects

B Scheel

Publications and source records attributed to B Scheel.

10 recordsLinked to original sources

PubMed2005

Human peripheral blood mononuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro.

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.

Antigen Presentation↗

PubMed2005

Follow-up and final results of the Oslo I Study comparing screen-film mammography and full-field digital mammography with soft-copy reading.

PURPOSE: To compare cancer detection rates of screen-film (SFM) and full-field digital mammography (FFDM) with soft-copy reading in a screening program including the initial positive scores for interval cancers and cancers in the subsequent screening round, and to analyze the false-negative FFDM interpretations. MATERIAL AND METHODS: Using a paired study design, 3683 women underwent SFM and FFDM in a population-based screening program. Two standard views of each breast were acquired. The images were interpreted without previous films for comparison. Independent double reading using a 5-point rating scale for probability of cancer was used for each modality. An examination was defined as positive if at least one of the two independent readers scored 2 or higher on the 5-point rating scale. SFM-positive cases were discussed in a SFM consensus meeting and FFDM-positive cases in a separate FFDM consensus meeting before recall. The study population was followed for more than 2 years so that interval cancers and screen-detected cancers in the subsequent screening round could be included. Cancer detection rates were compared using the McNemar test for paired proportions. The kappa statistic and Wilcoxon signed-rank test for matched pairs were used for comparing rating scores. The reading time was recorded for all FFDM interpretations. RESULTS: A total of 31 cancers (detection rate 0.84%) were diagnosed initially, of which SFM detected 28 and FFDM 23 (McNemar test P=0.23, discordant pair 8 and 3). Two cancers with a positive score at initial SFM reading and three with a positive score at initial FFDM reading were dismissed at SFM and FFDM consensus meetings, respectively. The difference in cancer detection after recall (discordant pair 11 and 5) was not significant (McNemar test, P=0.21). Of the 10 interval cancers and 16 screen-detected cancers in the subsequent round, 3 had true-positive SFM scores while 4 had true-positive FFDM scores in the initial reading session. A total of 38 cancers therefore had a positive result at double reading at one or both modalities, 31 at SFM and 27 at FFDM (McNemar test, P=0.48). Comparison of SFM and FFDM interpretations using the mean score for each case revealed no statistically significant difference between the two modalities (Wilcoxon signed-rank test for matched pairs; P-value=0.228). Two initial round cancers (one tumor found incidentally at work-up for a mass proved to be a simple cyst with a positive score at FFDM but a negative score at SFM, and one tumor with positive score at SFM but negative score at FFDM due to positioning failure) were excluded from the further analysis. Excluding these two cancers from comparison, there were 31% (22 of 72) false-negative SFM and 47% (34 of 72) false-negative FFDM individual interpretations. The overall mean interpretation time for normal FFDM examinations was 45 s. For most false-negative FFDM results, the reading time was shorter or longer than for normal examinations. The recorded FFDM interpretation time was noticeably short for several overlooked cancers manifesting as microcalcifications (ductal carcinoma in situ). CONCLUSION: There is no statistically significant difference in cancer detection rate between SFM and FFDM with soft-copy reading in a mammography screening program. Analysis of cancers missed at FFDM with soft-copy reading indicates that close attention has to be paid to systematic use of image display protocols.

Aged↗

PubMed2004

Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines.

In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked beta-globin untranslated region (UTR)-stabilized mRNA coding for beta-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.

Animals↗

PubMed2002

The GlnD and GlnK homologues of Streptomyces coelicolor A3(2) are functionally dissimilar to their nitrogen regulatory system counterparts from enteric bacteria.

Glutamine synthetase I (GSI) enzyme activity in Streptomyces coelicolor is controlled post-translationally by the adenylyltransferase (GlnE) as in enteric bacteria. Although other homologues of the Escherichia coli Ntr system (glnK, coding for a PII family protein; and glnD, coding for an uridylyltransferase) are found in the S. coelicolor genome, the regulation of the GSI activity was found to be different. The functions of glnK and glnD were analysed by specific mutants. Surprisingly, biochemical assay and two-dimensional PAGE analysis showed that modification of GSI by GlnE occurs normally in all mutant strains, and neither GlnK nor GlnD are required for the regulation of GlnE in response to nitrogen stimuli. Analysis of the post-translational regulation of GlnK in vivo by two-dimensional PAGE and mass spectrometry indicated that it is subject to both a reversible and a non-reversible modification in a direct response to nitrogen availability. The irreversible modification was identified as removal of the first three N-terminal amino acid residues of the protein, and the reversible modification as adenylylation of the conserved tyro-sine 51 residue that is known to be uridylylated in E. coli. The glnD insertion mutant expressing only the N-terminal half of GlnD was capable of adenylylating GlnK, but was unable to perform the reverse deadenylylation reaction in response to excess ammonium. The glnD null mutant completely lacked the ability to adenylylate GlnK. This work provides the first example of a PII protein that is modified by adenylylation, and demonstrates that this reaction is performed by a homologue of GlnD, previously described only as a uridylyltransferase enzyme.

Amino Acid Sequence↗

PubMed2000

Molecules on kepler orbits: An experimental study

We have demonstrated experimentally that polar molecules revolve around the inner electrode of a charged cylindrical capacitor in helical trajectories that result from a superposition of a translational motion along and an orbital motion around the cylinder axis. In this way molecular beams can be guided over any given distance. The results have been obtained for nozzle beams of NaCl, NaBr, and NaI seeded in Kr. The capacitor bent into a toroid may be used as a storage ring for polar molecules in high field seeking rotational states.

Journal Article↗

PubMed1995

[Extrapulmonary tuberculosis. An important differential diagnosis in immigrants with suspected malignancy].

The incidence of tuberculous disease is increasing all over the world, mostly in the poor, developing countries, but also in some industrialized countries. In Norway, extrapulmonary tuberculosis is a rare phenomenon. It is found mostly among older Norwegians and in younger immigrants from the third world. Since the disease is rare, it may be overlooked or confused with malignant disease. We describe two patients with unusual forms of extrapulmonary tuberculosis, both mimicking neoplastic disease. The first patient was a 27-year-old woman from South-East Asia, who was operated on for suspected intraductal comedo-type carcinoma of the breast, but histological examination showed tuberculous mastitis. The second patient was a 26-year-old man from East Africa with a medical history indicating intra-abdominal lymphoma. The final diagnosis, however, was mesenteric tuberculous lymphadenitis. Both patients were treated successfully with isoniazid, rifampicin and pyrazinamide.

Abdomen↗

PubMed1991

Circadian oscillations of nuclear-encoded chloroplast proteins in pea (Pisum sativum).

The diurnal and circadian expression of light-inducible chloroplast proteins, i.e. light-harvesting chlorophyll a/b protein (LHCP), early light-inducible protein (ELIP) and Fe-S Rieske, has been studied in young pea plantlets at the level of mRNA integrated into polysomal complexes and at the level of proteins. Under light-dark as well as constant light conditions the levels of the three nuclear-encoded chloroplast proteins oscillate while the investigated plastid-encoded proteins, large subunit of ribulose-1,5-bisphosphate carboxylase (LSU), reaction center protein D1 and cytochrome f, do not show oscillations at the protein level. The levels of the nuclear-encoded polysome-bound mRNAs fluctuate in parallel with the changes in the levels of poly(A) RNA which were described previously. Under constant light conditions the oscillation at the level of polysomal bound mRNA is readily dampened while the steady-state levels of the investigated nuclear-encoded proteins still fluctuate. We conclude that the extent of expression of the genes for the nuclear-encoded chloroplast proteins studied is controlled by a circadian ocillator primarily, but not exclusively, at the level of transcription.

Cell Nucleus↗

PubMed1990

A double-blind and randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke.

The effect of LMW heparin (Kabi 2165, Fragmin) was compared with placebo for the prevention of DVT in 103 patients with acute ischemic stroke using a prospective, double-blind, randomized trial design. Treatment was started within 72 hours, and LMW heparin was administered subcutaneously once daily according to body weight classes, which corresponded to about 55 to 65 Factor-Xa inhibitory U/kg, for 14 days, or until discharge from the hospital, if earlier. All patients underwent thrombosis surveillance with unilateral venography of the paretic limb. Evaluation of venography could be performed in 42 of 52 patients randomized to LMW heparin and in 50 of 51 patients randomized to placebo. The frequency of DVT was 15 of 42 patients or 36% (95% confidence interval 22 to 52%) in the LMW heparin group and 17 of 50 patients or 34% (21 to 49%) in the placebo group. The frequency of proximal thrombi was 5 of 42 (12%) and 8 of 50 (16%), respectively. There was one fatal pulmonary embolism in the placebo group. The mortality rate (28 days follow-up) was 5 of 52 in the LMW heparin group and 1 of 51 in the placebo group (p = 0.24). None of the deaths was related to treatment. No major hemorrhagic complications were observed. The mean Factor Xa inhibitory activity levels at peak concentration were 0.34 U/ml on day 2 and 0.42 U/ml on day 12 (p = 0.02). We conclude that LMW heparin in the dose range studied did not provide efficient prophylaxis against DVT in patients with acute ischemic stroke.

Acute Disease↗

PubMed1989

Focal changes of the spleen in one case of Gaucher disease--assessed by ultrasonography, CT, MRI and angiography.

Focal lesions of the spleen in one case of Gaucher disease are demonstrated by ultrasonography, CT, MRI and angiography. The sonographic and angiographic features differ from the findings presented in previous reports. The Gaucher manifestations in the spleen as demonstrated by CT, do not seem to have been reported previously. An earlier report on the MR findings in the liver and spleen in this disease did not disclose any focal abnormalities. In this case, ultrasonography and MRI revealed a targetlike configuration of the focal lesions. An attempt is made to analyze the more complex patterns disclosed by MRI against the background of the manifestations by the other imaging modalities and previous reports.

Angiography↗

PubMedDate not supplied

Increased detectability of liver metastases by the use of contrast enhancement in computed tomography. A comparison between the precontrast, the immediate postcontrast and the one hour postcontrast scan.

The precontrast, immediate postcontrast and the one hour postcontrast CT scans were analysed in search for liver metastases in 75 patients with malignant disease. The use of high dose intravenous contrast medium (42 g I) increased the number of hepatic metastases detected. The one hour postcontrast scan revealed a few more lesions than the immediate postcontrast scan. Further investigations on this subject are necessary before any definite conclusions can be made as our series of patients is small. In routine CT the most practical procedure in search for liver metastases is: 1) Scanning of the liver without contrast medium. 2) Incremental dynamic scanning during and immediately following injection of contrast medium. 3) If there is still uncertainty: Scanning at a later time, for example at one hour after injection of contrast medium.

Contrast Media↗