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G Jönsson

Publications and source records attributed to G Jönsson.

At least 19 recordsLinked to original sources
PubMed2006

Genomic profiling of bone and soft tissue tumors with supernumerary ring chromosomes using tiling resolution bacterial artificial chromosome microarrays.

Ring chromosomes and/or giant marker chromosomes have been observed in a variety of human tumor types, but they are particularly common in a subgroup of mesenchymal tumors of low-grade or borderline malignancy. These rings and markers have been shown to contain amplified material predominantly from 12q13-15, but also sequences from other chromosomes. Such amplified sequences were mapped in detail by genome-wide array comparative genomic hybridization in ring-containing tumor samples from soft tissue (n = 15) and bone (n = 6), using tiling resolution microarrays, encompassing 32 433 bacterial artificial chromosome clones. The DNA copy number profiles revealed multiple amplification targets, in many cases highly discontinuous, leading to delineation of large numbers of very small amplicons. A total number of 356 (median size: 0.64 Mb) amplicons were seen in the soft tissue tumors and 90 (median size: 1.19 Mb) in the bone tumors. Notably, more than 40% of all amplicons in both soft tissue and bone tumors were mapped to chromosome 12, and at least one of the previously reported recurrent amplifications in 12q13.3-14.1 and 12q15.1, including SAS and CDK4, and MDM2, respectively, were present in 85% of the soft tissue tumors and in all of the bone tumors. Although chromosome 12 was the only chromosome displaying recurrent amplification in the bone tumors, the soft tissue tumors frequently showed recurrent amplicons mapping to other chromosomes, that is, 1p32, 1q23-24, 3p11-12, 6q24-25 and 20q11-12. Of particular interest, amplicons containing genes involved in the c-jun NH2-terminal kinase/mitogen-activated protein kinase pathway, that is, JUN in 1p32 and MAP3K7IP2 (TAB2) in 6q24-25, were found to be independently amplified in eight of 11 cases with 12q amplification, providing strong support for the notion that aberrant expression of this pathway is an important step in the dedifferentiation of liposarcomas.

Adult↗
PubMed2006

Complement deficiency and disease: an update.

Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging from a Swedish study of C2 deficiency, a deficiency with an estimated prevalence of about 1/20,000 in Western countries, less than 10% of the deficiencies of the classical and alternative pathways and the late complement components are identified in Sweden. C1 inhibitor deficiency and deficiencies of MBL and MASP-2 were not included in the assessment. The introduction of new screening methods should facilitate detection of complement deficiencies in clinical practice. In our study of C2 deficiency (n=40), 57% of the patients had a history of invasive infection with encapsulated bacteria, mainly Streptococcus pneumoniae. This emphasizes the importance of the classical and/or the lectin pathway in defence against severe infection. Rheumatological disease, mainly systemic lupus erythematosus was present in 43% of the patients. In addition, a significant association was found between C2 deficiency and atherosclerosis. Complement-dependent disease mechanisms are discussed together with the potential importance of non-complement genes for disease expression in complement deficiencies. Analysis of larger patient groups is required in order to establish guidelines for investigation and treatment of patients with complement deficiency.

Atherosclerosis↗
PubMed2006

High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

Acute Disease↗
PubMed2006

Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel.

Whereas the involvement of Th1- and Th2-type cytokines in contact allergy to nickel (Ni) is well documented, the role of the regulatory cytokine IL-10 is less clear. We therefore investigated the impact of IL-10 on Ni-induced Th1- (IFN-gamma) and Th2-type (IL-4 and IL-13) cytokine responses in human peripheral blood mononuclear cells (PBMC). PBMC from 15 blood donors with reactivity to Ni (Ni-PBMC) and 8 control donors devoid of reactivity (control PBMC) were stimulated with Ni and the frequency of cytokine-producing cells and the levels of secreted cytokines were analysed by ELISpot (IL-4, IL-13 and IFN-gamma) and ELISA (IL-10, IL-13 and IFN-gamma), respectively. The Ni-induced response was further assessed in the presence of recombinant IL-10 (rIL-10) or neutralizing antibody to IL-10 and the phenotype of the Ni-specific cytokine-producing cells regulated by IL-10 was determined by cell depletion experiments. Ni induced IL-10 production in Ni-PBMC (mean, (range); 33.1 pg/ml (0-93.4 pg/ml)) but not control PBMC (2.2 pg/ml (0-14.9 pg/ml)) (P = 0.002). Ni also induced significant production of IL-4, IL-13 and IFN-gamma that correlated with the IL-10 response. Addition of rIL-10 down-regulated the Ni-induced production of all cytokines but with a more pronounced effect on IFN-gamma. However, neutralization of Ni-induced IL-10 enhanced the levels of IFN-gamma induced by Ni (P = 0.004) but did not affect the number of IFN-gamma-producing cells or the production of other cytokines. Cell depletion experiments suggested that the Ni-specific IFN-gamma (and Th2-type cytokine) producing cells were CD4(+) T cells. The impact of IL-10 on Ni-induced IFN-gamma responses by CD4(+) T cells suggests that an important role of IL-10 in vivo is to counteract the allergic reactions mediated by Th1-type cytokines.

Allergens↗
PubMed2005

Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis.

OBJECTIVE: To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. METHODS: Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. RESULTS: Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. CONCLUSIONS: Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.

Adolescent↗
PubMed2001

Studies of the radon concentration in drinking water from the horst Söderåsen in southern Sweden.

The radon activity concentration in ground water from drilled and dug wells on the horst Söderåsen in Southern Sweden has been determined with two different methods, gamma activity measurements with a germanium HPGe detector and alpha activity measurements with plastic track detectors. The results are consistent. High activity concentration is connected to granite bedrock. Dug wells have low concentrations and no trivial correlation between concentration and depth of the well is found. Large local variations exist. Activity concentrations > 700 Bq/l appear to be associated with leakage from layers of volcanic origin. The concentration from drilled wells is found to be quite constant over a 3 year period but short time variations appear to be significant. Evaporation from the open surface of a normal cooking vessel is slow with an activity gradient delta A/A of about 0.1-0.2 per hour at room temperature whereas even modest heating of water in e.g. a coffee machine is very efficient and reduces the radon activity concentration by > 90% in one process.

Radon↗
PubMed2000

Frequency of penicillin-resistant pneumococci in children is correlated to community utilization of antibiotics.

OBJECTIVE: To study the impact of the utilization of antibiotics in children at the population level on the frequency of penicillin-nonsusceptible pneumococci (PNSP). DESIGN: Children ages 0 to 6 years with a nasopharyngeal culture of PNSP were registered on place of residency in the 20 municipalities of the former Malmöhus County (since 1998 a part of Skåne County). Where possible the total number of nasopharyngeal cultures with growth of pneumococci was registered as well. All antibiotic prescriptions for 0- to 6-year-old children were analyzed in the 20 municipalities. MAIN OUTCOME MEASURES: Correlation between the utilization of antibiotics and the frequency of PNSP in children at the municipality level. RESULTS: The proportion of PNSP among all isolates of pneumococci from nasopharyngeal cultures varied between 0 and 49.5%. The antibiotic utilization in children varied among the 20 neighboring municipalities from 8.5 to 19.7 defined daily doses per 1000 children per day. The municipalities with high total utilization also had more frequent use of macrolides and broad spectrum antibiotics. The was a significant correlation between antibiotic use and the proportion of PNSP (correlation coefficient, 0.96; P = 0.002), and the correlation coefficients for trimethoprim-sulfamethoxazole, amoxicillins, macrolides and cephalosporins were significant at the 0.001 level. There was no significant correlation between the use of penicillin V and the frequency of PNSP. CONCLUSIONS. There was a significant correlation between the frequency of PNSP and the utilization of antibiotics in children at the population level.

Anti-Bacterial Agents↗
PubMed2000

Cellular changes and apoptosis in the spleens and peripheral blood of mice infected with blood-stage Plasmodium chabaudi chabaudi AS.

Infection with blood-stage Plasmodium chabaudi chabaudi AS results in splenomegaly, peripheral leukocytosis, and a major activation of the immune system. The frequencies and absolute numbers of T-cell, B-cell, and macrophage populations in spleen and peripheral blood from P. chabaudi-infected BALB/c mice were compared and found to be significantly altered during acute infection. The kinetics of the redistribution of the different cell types in spleen and peripheral blood were different, with T and B cells appearing in the blood when their frequencies and absolute numbers in the spleen were low. The frequency and absolute number of apoptotic cells in the spleen were increased during acute P. chabaudi infection and involved both T cells, B cells, and macrophages. Both Fas and Fas-ligand expression were increased in the spleen. Taken together, our data provide new information on the complex cellular interactions that take place in the immune system during blood-stage malaria infection in a mouse model.

Acute Disease↗
PubMed1998

Stimulation of CD40 in human bladder carcinoma cells inhibits anti-Fas/APO-1 (CD95)-induced apoptosis.

CD40 and the CD95 (Fas/APO-1 antigen) are both members of the tumor necrosis factor receptor family. Whereas CD40 mediates a strong growth stimulatory signal in B cells, engagement of the CD95 receptor leads to growth inhibition and induction of apoptosis. As it has been reported that CD40 activation may rescue B cells from undergoing apoptosis, we were interested to see whether it had a similar effect in other cells expressing the CD40 receptor. We used epithelial tumor cells from the urinary bladder, a cell type that frequently expresses CD40 but for which no clear function of the molecule has been assigned. We found that the ligation of CD95 with the antibody anti-APO-1 induced apoptosis in most of the cell lines tested. Stimulation of CD40 with antibodies or a soluble construct of the CD40 ligand was shown to protect cells from apoptosis, as demonstrated by their ability to suppress the growth inhibition exerted by the anti-APO-1 antibody. Our results show that CD40 stimulation make cells less vulnerable to apoptosis induced via CD95 and suggest that CD40 expression on epithelial tumors may be associated with cell survival.

Animals↗
PubMed1998

The use of a conical fixture design for fixed partial prostheses. A preliminary report.

A specially designed, TiO2-blasted titanium fixture, partially conical and microthreaded, the Astra Tech Fixture ST, was used for rehabilitation of partial edentulism in the posterior mandible. Superior to the mandibular canal 25 fixtures were placed in 10 patients. Fixed metal-ceramic bridges were then performed. After 1-year follow-up, all bridges were found to be clinically stable. The implant survival rate was 100% and the mean marginal bone resorption was 0.05 +/- 0.11 mm.

Aged↗
PubMed1996

Phosphorous carbohydrates on chimeric CD22, CD44 and CD62L.

There are few examples of phosphorous carbohydrates described in higher animals. Here we have used recombinant molecules where the extracellular part of membrane receptors have been fused with the Fc part of human IgG (Rg-chimeras) to look at the prevalence of phosphorous carbohydrates. Also chimeras of a few hormones were used in this study. Thirteen Rg constructs were transfected into Cos cells and labelled with [32P]orthophosphate in phosphor deficient media. These Rg molecules were subsequently purified on protein A-Sepharose and submitted to SDS-PAGE and radiography. CD22Rg, CD62L-Rg and CD44Rg were all labelled very strongly with 32P. From CD22Rg and CD62L-Rg the label could be easily removed by N-glycosidase F, but the 32P label on CD44Rg was resistant to N-glycosidase treatment. However, after treatment with O-glycosidase combined with sialidase, CD44Rg retained only a fraction of the 32P. Weakly phosphorylated Rg molecules were CD62E-Rg and CD7Rg. However, CD7Rg did not seem to loose the label, only shift position after N-glycosidase treatment and CD62E-Rg did neither shift position nor loose any 32P label after the N-glycosidase treatment. Negative chimeras were CD40Rg, CD33Rg, Lamp-1Rg, CD34Rg, ICAM-1Rg, TNF alpha Rg, CD19Rg and CD5Rg. The phosphate label of CD22Rg was completely removed after ALP treatment and in CD44Rg most of the label was removed. ALP is not supposed to cleave phosphodiesterbonds leading to the conclusion that the phosphor is likely present in the form of phosphomonoesters. This result is interesting as alkaline phosphatase (ALP) is common on the outer cellsurface of many cell types and might interact with phosphorous carbohydrates on membrane proteins. The membrane from of CD22 was also transfected into Cos cells and labelled with 32P in phosphate free media. Subsequently the cells were lysed and CD22 affinity purified and analysed by SDS-PAGE and radiography. Under these conditions CD22 was shown to be 32P labelled, but only 20% of the label was removed by N-glycosidase F treatment. These results do not show that CD22, CD44 and CD62L are phosphorylated on carbohydrates under more physiological circumstances, but they do show that phosphorous carbohydrates might be more common in higher animals than what was been reported.

Antigens, CD↗
PubMed1995

Intestinal microbial bile acid transformation in healthy infants.

Following the establishment of functionally active intestinal flora in three healthy Swedish children from birth up to 24 months of age, we investigated the development of different 24-carbon bile acids. The fecal bile acids were group-separated into unconjugated, glycine-conjugated, taurine-conjugated, and sulfated, so that we could follow the changes between the different fractions of conjugates. In meconium, most (55-63%) of the bile acids were conjugated with taurine; only 11-32% were conjugated with glycine. Deconjugation was the first sign of intestinal microbial activity on the bile acids. Already at 1 month of age, most of the bile acids were deconjugated; among the conjugated bile acids, the glycine-conjugated dominated over the taurine-conjugated. An unidentified conjugate of cholic and chenodeoxycholic acids (C, CDC) that separated with the sulfated bile acids was found. The unconjugated bile acids and those that arose from hydrolysis of existing conjugates were separated and identified by gas-liquid chromatography coupled to mass spectrometry (GC-MS). Twenty-nine different bile acids were identified. In meconium, 16 different bile acids were identified. C and CDC were identified in all samples. The bile acid pattern changed during the course of the study. Many of the identified bile acids were only found in one or a few of the analyzed samples, and sometimes only in samples from one child. 6 alpha-hydroxylated bile acids, probably not microbially synthesized, were present at high percentages in the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Bifidobacterium↗
PubMed1995

Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver.

Budesonide is a synthetic glucocorticosteroid that is commonly used in topical treatment of asthma and rhinitis. The main metabolites formed from budesonide in human liver microsomes have been identified as 16 alpha-hydroxyprednisolone and 6 beta-hydroxy-budesonide. Although it is apparent that the cytochrome P450 (CYP) system is involved, the actual subfamily has not been identified. In attempts to do this, budesonide was incubated with microsomes from ten different human liver samples where various CYP activities had been rank ordered. We found a strong correlation between formation of the two main metabolites and testosterone 6 beta-hydroxylation (correlation 0.98 and 0.95), a marker for CYP3A. When budesonide (10 microM) was incubated with human liver microsomes in the presence of compounds known to interact with different isoforms or subfamilies of CYP, ketoconazole was found to be the strongest inhibitor of budesonide metabolism (IC50: approximately 0.1 microM) followed by troleandomycin (IC50: approximately 1 microM), erythromycin, and cyclosporin, all substances known to interact with CYP3A isoenzymes. Substances known to interact with CYP2C (sulfaphenazole, mephenytoin, and tolbutamide) and with CYP2D6 (bufuralol and quinidine) did not specifically inhibit the metabolism of budesonide. In addition, formation of the budesonide metabolites (16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide) was inhibited by antibodies against the CYP3A subfamily, but not by antibodies against the CYP1A subfamily or control immunoglobulin G. We conclude that the formation of 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide from budesonide is catalyzed by isoenzymes within the CYP3A subfamily.

Administration, Topical↗
PubMed1994

Concentrations of sodium, potassium, calcium, magnesium and chlorine in the muscle cells of downer cows and cows with parturient paresis.

The concentrations of sodium, potassium, calcium, magnesium, phosphorus, sulphur and chlorine, in the skeletal muscle fibres of cows with parturient paresis, downer cows, normally calving cows and unmated heifers were determined by means of an X-ray microanalysis technique. The most consistent finding was an increase in the concentration of chlorine in the muscle samples from the downer cows. There were no other significant differences between the concentrations of these elements in samples from the different groups of cows, but the calcium concentration was higher in the muscle samples collected one month after parturition than in the samples collected close to parturition.

Animals↗
PubMed1993

Indoor radon-daughter concentration and gamma radiation in urban and rural homes on geologically varying ground.

The radon (Rn)-daughter level (track film, 3 months) was lower in 129 urban than in 197 rural houses (geometric means, (GM) 18 versus 40 Bq/m3; P < 0.001; range 3-416). In rural dwellings higher levels were found in those built over deposits of alum shale occurrences (P = 0.04; 12 on porous glaciofluvial cover 94 Bq/m3; 127 others 43 Bq/m3; significant interaction, P = 0.01), than in 158 others (37 Bq/m3). There was no systematic effect of the type of water supply, neither of indoor smoking. One hundred twenty three homes with a complete cellar were lower than 200 with no or part cellar (18 versus 40 Bq/m3; P < 0.001). There was only a weak association between log-transformed gamma radiation (GM 10, range 33-50 microR/h) and Rn-daughter levels (r = 0.18; 95% confidence interval 0.07-0.28). Our results show the importance for indoor Rn-daughter levels of the bedrock and cover beneath the house, and the need for Rn-daughter measurements in epidemiological studies.

Air Pollution, Indoor↗
PubMed1993

Ultrasonography and determination of proteins and enzymes in blood for the diagnosis of liver abscesses in intensively fed beef cattle.

The concentrations of plasma proteins and the activities of liver enzymes were measured every 2 weeks from weaning to slaughter in 21 beef cattle, and their livers were examined ultrasonographically every 4 weeks. Eight of the 9 cases of single or multiple liver abscesses were detected by ultrasonography but some individual abscesses, particularly those in the left side of the liver, remained undetected. The time at which the abscesses were first detected ranged from 4 to 20 (mean 12.5) weeks. There were only slight variations in the blood constituents and they were of no significant value in the diagnosis of the liver abscesses.

Animal Feed↗