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Biomedical subjects

C Möller

Publications and source records attributed to C Möller.

At least 19 recordsLinked to original sources
PubMed2006

IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family members.

Activation of the high-affinity IgE-receptor, FcepsilonRI, expressed on mast cells can result in either enhanced survival or apoptosis depending on the circumstances. In this study, we have analysed signalling pathways involved in the regulation of mast cell survival and apoptosis. FcepsilonRI cross-linking induces phosphorylation of Akt and its downstream target forkhead transcription factors. In addition, Bad, GSK-3beta and IkappaB-alpha also become phosphorylated. A1, a prosurvival Bcl-2 homologue transcriptionally controlled by NFkappaB transcription factors, is upregulated upon FcepsilonRI activation. These events have prosurvival effects on the mast cells. Moreover, FcepsilonRI activation upregulates the levels of the proapoptotic protein Bim and induces a rapid, but transient, phosphorylation of Bim. Thus, FcepsilonRI activation of mast cells leads to both prosurvival and proapoptotic signalling events where the outcome most likely depends on the balance between these signals.

Animals↗
PubMed2006

IgE-receptor activation induces survival and Bfl-1 expression in human mast cells but not basophils.

BACKGROUND: The contribution of mast cells to the pathology of allergic diseases are facilitated by their long life span in tissue and ability to regranulate. Bcl-2 genes are one of the main regulators of cell death and survival. The aim of this study was to elucidate the mechanisms responsible for mast cell survival in allergy. METHODS: Bcl-2 family gene expression in human mast cells and basophils was analyzed by ribonuclease protection assay and by reverse-transcriptase polymerase chain reaction. Cell survival was measured by mixing cells with the vital dye, trypan blue, and the number of living cells was enumerated. Apoptotic cells were measured by a Cell Death Detection ELISA. RESULTS: We found that cross-linking of FcepsilonRI on human cord blood cultured mast cells (CBCMCs) promoted cell survival and induced expression of the pro-survival gene Bfl-1. CBCMCs were found to express both Bfl-1 and Bfl-1S, two splicing variants of Bfl-1. Bfl-1 induction was mediated through Syk, PI3-kinase and intracellular calcium mobilization, since piceatannol, wortmannin and EDTA, respectively, significantly reduced Bfl-1 expression levels. In contrast to CBCMCs, no evidence was found for Bfl-1 expression and survival promotion in human basophils. CONCLUSIONS: Immunoglobulin E (IgE)-dependent activation-induced mast cell survival was correlated with Bfl-1 gene upregulation, providing a possible explanation for mast cell longevity in allergic reactions.

Basophils↗
PubMed2006

Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children.

BACKGROUND: A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up--2 years after termination of immunotherapy. METHODS: A total of 183 children, aged 6-14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation. RESULTS: The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5-year follow-up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow-up period in the control patients. The immunotherapy-treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores (P < 0.01). CONCLUSION: Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long-term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.

Adolescent↗
PubMed2004

Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and Russia.

AIM: The main aim of the study was to describe the differences between some Northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms. METHODS: At the participating clinics, patients with a history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire in which 86 different foodstuffs were listed. Skin-prick tests (SPT) were performed with common inhalant allergens. RESULTS: The foods that were reported as eliciting symptoms differed between countries. In Russia, Estonia, and Lithuania; citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, egg, and milk were most often reported as causes of hypersensitivity. In Sweden and Denmark; birch pollen (BP) related foods, such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common causes. In all countries, children, more often than adults, had symptoms of allergic reaction to citrus fruits, tomato, strawberry, milk, egg, and fish. Most patients (95%) reported hypersensitivity to several foodstuffs (median: eight foods). The most common symptoms were oral allergy syndrome and urticaria. Severe symptoms were most common with fish, shellfish, nuts, and milk. Slight symptoms were most common with rice, coriander, poppy seed, lingonberry, corn, caraway red currant, and fig. Earlier well-known correlations, such as that between BP sensitization and some fruits and vegetables, as well as that between mugwort and some spices, were conoborated. Positive correlations were found between self-reported hypersensitivity to crustaceans and SPT with horse. A negative correlation was seen between hypersensitivity to crustaceans and SPT with BP. CONCLUSIONS: The foodstuffs that often are reported to cause food hypersensitivity, differ between Sweden/Denmark on one side and the Baltic States and Russia on the other. BP-related foods dominate in Scandinavia, whereas some mugwort-related foods are of more importance in Russia and the Baltic States.

Adolescent↗
PubMed2003

Expression and function of chemokine receptors in human multiple myeloma.

Multiple myeloma (MM) is a B cell tumor characterized by its selective localization in the bone marrow. The mechanisms that contribute to the multiple myeloma cell recruitment to the bone marrow microenvironment are not well understood. Chemokines play a central role for lymphocyte trafficking and homing. In this study we have investigated expression and functional importance of chemokine receptors in MM-derived cell lines and primary MM cells. We found that MM cell lines express functional CCR1, CXCR3 and CXCR4 receptors, and some also CCR6. Although only a minority of the cell lines responded by calcium mobilization after agonist stimulation, a migratory response to the CCR1 ligands RANTES and MIP-1 alpha was obtained in 5/6 and 4/6, respectively, of the cell lines tested. Five out of six cell lines showed a response to the CXCR4 ligand SDF-1. In addition, 3/6 cell lines migrated in response to MIP-3 alpha and IP-10, ligands for CCR6 and CXCR3, respectively. The expression of CXCR4 and CCR1 and the migration to their ligands, SDF-1, and RANTES and MIP-1 alpha, respectively, were also demonstrated in primary MM cells. These findings suggest that chemokine receptor expression and the migratory capacity of MM cells to their ligands are relevant for the compartmentalization of MM cells in the bone marrow.

Calcium↗
PubMed2003

Safety of nasal budesonide in the long-term treatment of children with perennial rhinitis.

BACKGROUND: Intranasal budesonide is an efficacious treatment for perennial allergic rhinitis. Long-term effects on safety, particularly in children, need further investigation. OBJECTIVE: To investigate the long-term safety of intranasal budesonide in children. METHODS: In an open trial, 78 children (5-15 years) with perennial rhinitis were treated with intranasal budesonide pressurized metered dose inhaler 200 microg twice daily (delivered daily dose 256 microg) for 12 months; 43 children stayed in the study for 12 additional months and were switched to aqueous suspension (400 microg delivered daily dose) for 6 months. Statural growth, bone age, ophthalmologic and rhinoscopic status, cortisol and biochemical analyses in blood and urine were monitored during the first and second years, and adverse events (AEs) were continuously recorded. RESULTS: No significant effects on statural growth and bone age, compared with reference values, were observed. Morning plasma cortisol and 24-h urinary cortisol were not changed during treatment. Patients reported 195 AEs, most commonly nasal dryness (30%), blood-tinged secretions (21%) and, among non-nasal AEs, headache (13%). Rhinoscopy revealed no signs of mucosal atrophy, ulceration, or candidiasis but some nasal dryness. No treatment-related ophthalmological or biochemical aberrations were found. Reduction of blood eosinophils and nasal symptom scores, compared with pre-treatment values, indicated the efficacy of budesonide treatment. CONCLUSION: Long-term treatment for 1-2 years with intranasal budesonide 256-400 microg daily in children with perennial rhinitis revealed no negative effects on growth or endogenous cortisol production. Local side-effects were mild and patient symptoms decreased.

Administration, Intranasal↗
PubMed2003

Activation of mast cells by immunoglobulin E-receptor cross-linkage, but not through adenosine receptors, induces A1 expression and promotes survival.

BACKGROUND: Mast cells are a potent source of mediators that regulate the inflammatory response in allergy and asthma. Mast cells can be activated through different receptors, for example, via cross-linkage of the high-affinity IgE receptor (Fc epsilon RI) and by adenosine acting on specific receptors. We have recently described mast cell survival of an IgE receptor activation by up-regulation of the anti-apoptotic gene A1. OBJECTIVE: To compare mast cell survival and expression of A1 after activation through the Fc epsilon RI and by an adenosine agonist. METHODS: Bone marrow-derived, cultured mouse mast cells (BMCMC) were activated either with IgE+antigen or with the adenosine receptor agonist 5'-N-ethylcarboxamido adenosine (NECA). Release of beta-hexosaminidase, cell viability, phosphorylation of Akt and IkB-alpha, and expression of pro-survival and pro-apoptotic genes were measured after activation. RESULTS: Activation of BMCMC with NECA caused the release of beta-hexosaminidase, although to a lesser extent than after Fc epsilon RI activation (33% and 98%, respectively). Activation by both NECA and Fc epsilon RI stimulated phosphorylation of Akt (Ser473 and Thr308) and IkB-alpha (Ser32), both of which are implicated in the regulation of cell survival. However, only cells that were activated through Fc epsilon RI, but not by NECA, expressed A1 and exhibited an increased survival rate compared to the control. CONCLUSION: These results show that adenosine receptor activation of BMCMC does not induce the same survival programme in mast cells as does activation through Fc epsilon RI. These findings may be important for understanding the role that mast cells play in asthma provoked by different stimuli.

Adenosine↗
PubMed2003

The hazards of kissing when you are food allergic. A survey on the occurrence of kiss-induced allergic reactions among 1139 patients with self-reported food hypersensitivity.

BACKGROUND: According to a few case reports, kissing can induce symptoms due to food allergy. OBJECTIVE: We wanted to investigate the occurrence of kiss-induced allergic symptoms and other social inconveniences among patients with self-reported food hypersensitivity. METHODS: A questionnaire was answered by 1139 patients (1-84 years old, mean age 29 years, 393 males and 746 females) who considered themselves to be food allergic. RESULTS: 12% of the patients experienced allergic symptoms when in close contact with (e.g., kissing) a person who had eaten a nontolerated food prior to the contact. Some case histories suggested that the symptoms only appeared if the food intake had occurred immediately before the kiss. In addition, the questionnaires showed that 55% had problems in daily life finding tolerable food, 44% were afraid of a severe reaction from eating nontolerated food, 13% could experience symptoms when sitting beside a person who was eating such a food, and 17% could experience symptoms in the kitchen when someone else was preparing such food. CONCLUSIONS: What other people eat can influence the quality of life of food-allergic patients.

Adolescent↗
PubMed2002

Sampling effects influence heights measured with atomic force microscopy.

The atomic force microscope (AFM) is an exquisitely delicate probe measuring the height of a specimen at discrete sampling points in a fixed two-dimensional (2D) raster. The resulting topograph is a 2D digital image, with each pixel representing a distinct height measurement. The height of an object is determined as the average of the maximum heights measured above the supporting surface. We show that such object heights derived from a variety of organic samples depend critically on the sampling or pixel size of the 2D raster. It is concluded that to obtain accurate specimen heights, the pixel size must be small enough to resolve submolecular structures and thus ensure representative sampling of the height variation on the surface.

Bacillus Phages↗
PubMed2002

Non-viral mediated gene transfer of porphobilinogen deaminase into mammalian cells.

Acute intermittent porphyria (AIP) is an inborn error of heme synthesis in which the third enzyme, porphobilinogen deaminase (PBGD), is deficient. The disease is characterized by recurrent attacks of acute abdominal pain often accompanied by neuropsychiatric symptoms. Current therapeutic treatment with heme is only palliative and no curative alternative exists. The present report describes the first step towards a gene therapy treatment for AIP. Mouse cDNA encoding the PBGD enzyme was cloned and four vectors containing the full-length mouse and human cDNA of the housekeeping and erythroid PBGD isoforms under the control of a cytomegalovirus promoter were constructed. The vectors, condensed to polyethylenimine, were successfully transfected to NIH 3T3 and HeLa cells as determined by enzymatic activity measurements. Thus, the PBGD activity was increased 3-10 times in NIH 3T3 cells and 95-240 times in HeLa cells. The expression was shown to be dose and time dependent, with the highest level of activity observed in HeLa cells after 72 h posttransfection. Non-viral gene transfer was also undertaken in PBGD-deficient fibroblasts established from an AIP patient. Complete normalization of the PBGD activity was accomplished after the addition of 2.5 microg DNA per well. Further addition of DNA increased the PBGD activity up to threefold the normal value. The study documents a successful gene transfer and a high degree of PBGD expression in different cell-lines, indicating a potential for future gene therapy in AIP.

3T3 Cells↗
PubMed2001

Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation.

Mast cells reside in tissues, where upon activation through the high-affinity-IgE-receptor (FcepsilonRI) they degranulate and orchestrate the allergic reaction. Mast cells survive this activation and can thus be reactivated. In this study we demonstrate that this process depends on the pro-survival gene A1. Activation of mast cells through FcepsilonRI resulted in degranulation, strong induction of A1 mRNA and protein, and cell survival. In contrast, A1-deficient mast cells released granule mediators similar to the wild-type control, but the cells did not survive an allergic activation. Furthermore, A1(-/-) mice that had been sensitized and provoked with allergen exhibited a lower number of mast cell compared with littermate controls. The induction of A1 was dependent on calcium, as EDTA prevented A1 expression. The calcium ionophore, ionomycin, induced A1 expression and mast cell survival, whereas compound 48/80, a well-known mast cell secretagogue, did not. This study uncovers the importance of A1 for mast cell survival in allergic reactions, and it proposes A1 as a potential target for the treatment of allergic diseases.

Animals↗
PubMed2001

Chemical modification of transducin with iodoacetic acid: transducin-alpha carboxymethylated at Cys(347) allows transducin binding to Light-activated rhodopsin but prevents its release in the presence of GTP.

Modification of transducin (T) with iodoacetic acid (IAA) inhibited its light-dependent guanine nucleotide-binding activity. Approximately 1 mol of [(3)H]IAA was incorporated per mole of T. Cys(347), located on the alpha-subunit of T (T(alpha)), was identified as the major labeled residue in the [(3)H]IAA-modified holoenzyme. In contrast, Cys(135) and Cys(347) were modified with [(3)H]IAA in the isolated T(alpha). IAA-modified T was able to bind tightly to photoexcited rhodopsin (R*), but GTP did not promote the dissociation of the complex between alkylated T and R*. In addition, R* protected against the inhibition of T by IAA. A comparable inactivation of T and analogous interactions between T and R* were observed when 2-nitro 5-thiocyanobenzoic acid (NTCBA) was used as the modifying reagent (J. O. Ortiz and J. Bubis, 2001, Effects of differential sulfhydryl group-specific labeling on the rhodopsin and guanine nucleotide binding activities of transducin, Arch. Biochem. Biophys. 387, 233-242). However, while carboxymethylated T was capable of liberating GDP in the presence of R*, NTCBA-modified T was unable to release the guanine nucleotide diphosphate upon incubation with the photoactivated receptor. Thus, IAA-labeling stabilized a T:R* complex intermediate carrying the empty nucleotide pocket conformation of T. On the other hand, NTCBA-modified T seemed to be "locked" in the GDP-bound state of T, even in the presence of R*.

Animals↗
PubMed2001

A common ancestral origin of the frequent and widespread 2299delG USH2A mutation.

Usher syndrome type IIa is an autosomal recessive disorder characterized by mild-to-severe hearing loss and progressive visual loss due to retinitis pigmentosa. The mutation that most commonly causes Usher syndrome type IIa is a 1-bp deletion, described as "2299delG," in the USH2A gene. The mutation has been identified in several patients from northern and southern Europe and from North America, and it has been found in single patients from South America, South Africa, and China. Various studies have reported a range of frequencies (.16-.44) among patients with Usher syndrome, depending on the geographic origin of the patients. The 2299delG mutation may be the one that most frequently causes retinitis pigmentosa in humans. Given the high frequencies and the wide geographic distribution of the mutation, it was of interest to determine whether the mutation resulted from an ancestral mutational event or represented a mutational hotspot in the USH2A gene. Haplotype analysis was performed on DNA samples from 116 unrelated patients with Usher syndrome type IIa; the patients were from 14 countries and represented 148 2299delG alleles. On the basis of six single-nucleotide polymorphisms within the USH2A gene, 12 core haplotypes were observed in a panel of normal chromosomes. However, in our analysis, only one core haplotype was found to be associated with the 2299delG mutation. The data indicate that the widespread geographic distribution of the 2299delG mutation is the result of an ancestral mutation that has spread throughout Europe and into the New World as a result of migration.

Alleles↗
PubMed2001

Neonlike iron x-ray laser: population kinetics and radiative transfer.

In this work, we present collisional-radiative calculations for neonlike iron x-ray lasers. These calculations show the importance of the interaction between the x-ray laser beam and the amplifying medium, which is taken into account in the paraxial Maxwell-Bloch approach. Our calculations are in better agreement with a recent experiment (a prepulse plus two main pulses) on the 3p-3s 0-1 line, than the code EHYBRID which ignores the above interaction. Saturation is attained for plasma lengths near 1 cm, and the calculated effective gain agrees with the experimental value, at least for the first main pulse.

Journal Article↗
PubMed2001

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

Adolescent↗
PubMed2001

From images to interactions: high-resolution phase imaging in tapping-mode atomic force microscopy.

In tapping-mode atomic force microscopy, the phase shift between excitation and response of the cantilever is used as a material-dependent signal complementary to topography. The localization of information in the phase signal is demonstrated with 1.4-nm lateral resolution on purple membrane of Halobacterium salinarum in buffer solution. In a first-order approximation, the phase signal is found to correlate with modulations of the tip oscillation amplitude, induced by topography. Extending the analysis to contributions of the tip-sample interaction area as a second-order approximation, a method is proposed to extract information about the interaction from the phase signal for surfaces with a roughness in the order of the tip radius.

Buffers↗
PubMed2001

Local 5,7-dihydroxytryptamine lesions of rat amygdala: release of punished drinking, unaffected plus-maze behavior and ethanol consumption.

Several serotonergic drugs are effective for anxiety disorders, but underlying mechanisms are unclear, and findings in experimental animals are difficult to reconcile with human data. It has been proposed that differential effects of serotonin within specific anatomical systems may account for these difficulties, and the amygdala has been suggested as one of the structures involved. To examine this hypothesis, the neurotoxin 5,7-dihydroxytryptamine was administered locally in rat amygdala. Within the amygdala, serotonin was depleted by approximately 80%, with other transmitters unaffected, and serotonin transporter labelling was decreased by approximately 85%. Cortical areas near the lesion site were also affected, although to a lesser degree. Other forebrain areas were unaffected. Lesions resulted in a specific anti-conflict effect in a punished drinking test, but did not influence elevated plus-maze behavior (under baseline conditions and after restraint stress), locomotor activity or ethanol intake. These data suggest that the punished drinking test and the elevated plus-maze may activate different components of fear circuitry, and that the serotonergic input to the amygdala specifically participates in fear-related behavioral suppression mediated by this structure.

5,7-Dihydroxytryptamine↗