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Biomedical subjects

G Nilsson

Publications and source records attributed to G Nilsson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Evaluation of three Swedish ICD-10 primary care versions: reliability and ease of use in diagnostic coding.

If computer-stored information is to be useful for purposes other than patient care, reliability of the data is of utmost importance. In primary healthcare settings, however, it has been found to be poor. This paper presents a study on the influence of coding tools on reliability and user acceptance. Six general practitioners coded 152 medical problems each by means of three versions of ICD-10, one with a compositional structure. At code level the reliability was poor and was almost identical when the three versions were compared. At aggregated level the reliability was good and somewhat better in the compositional structure. Ideas for improved user acceptance arose, and the study explored the need for several different tools to retrieve diagnostic codes.

Analysis of Variance↗
PubMed1999

Expression of insulin-like growth factor-1 receptor in synovial sarcoma: association with an aggressive phenotype.

It is well known that insulin-like growth factor-1 receptor (IGF-1R) plays a crucial role in proliferation and survival of transformed cells. Overexpression of IGF-1R in certain tumors has been reported, but there is still little known about its importance in vivo. Here, we evaluated the IGF-1R levels in 35 human synovial sarcoma tumors by Western blot and reverse transcriptase-PCR. In 18 of these, IGF-1R was detectable by Western blot, whereas 17 were nondetectable. There was a significant association between the amount of receptor proteins and mRNA transcripts. Furthermore, we found that the IGF-1R Western blot-positive tumors were associated with a high incidence of lung metastases. Eleven of 18 (61%) developed metastases in the IGF-1R detectable group, compared to 3 of 17 (18%) in the nondetectable group (P = 0.01). Moreover, in the detectable group of IGF-1R, 12 of 18 (67%) exhibited a high tumor cell proliferative rate, compared to 5 of 16 (31%) in the nondetectable group (P = 0.04). On the other hand, no association was found between the IGF-1R and type of fusion gene transcript (SYT-SSX1 or SYT-SSX2). Our results suggest that expression of IGF-1R can underlie an aggressive phenotype in synovial sarcoma.

Adult↗
PubMed1999

The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome.

Cytogenetically, synovial sarcoma (SS) is characterized by the translocation t(X;18)(p11.2;q11.2), resulting in a fusion between the SYT gene on chromosome 18 and SSX1 or SSX2 on the X chromosome and the formation of new chimeric genes, SYT-SSX1 or SYT-SSX2. We examined the potential clinical relevance of SYT-SSX1 and SYT-SSX2 fusion transcripts together with tumor proliferation. In a series of 33 patients with primary SS, the type of fusion transcript was assessed by reverse transcription-PCR and sequence analysis. The proliferation rate was analyzed using anti-Ki-67 antibodies. One case carrying an atypical transcript with a 57-bp insert was excluded, leaving 13 SYT-SSX1 and 19 SYT-SSX2 cases for analysis. The hazard ratio (with respect to metastasis-free survival for patients with SYT-SSX1 versus patients with SYT-SSX2 fusion transcripts was 7.4 (95% confidence interval, 1.5-36; log-rank P = 0.004). There was also an association with reduced overall survival for patients with SYT-SSX1 compared to patients with SYT-SSX2 (hazard ratio, 8.5; 95% confidence interval, 1.0-73; log-rank P = 0.02). The 5-year metastasis-free survival for patients with SYT-SSX1 was 42% versus 89% for patients with SYT-SSX2. There was a significant association between SYT-SSX1 and a high tumor proliferation rate (P = 0.02). We conclude that the findings suggest that the type of SYT-SSX fusion transcript determines the proliferation rate and is an important predictor of clinical outcome in patients with SS.

Adolescent↗
PubMed1999

Mast cell migratory response to interleukin-8 is mediated through interaction with chemokine receptor CXCR2/Interleukin-8RB.

To explore the role of chemokines in mast cell chemotaxis and accumulation at sites of inflammation, we first investigated the response of human mast cells to 18 different chemokines by induction of intracellular calcium mobilization in the human mast cell line, HMC-1. Only a subgroup of CXC chemokines defined by the conserved sequence motif glutamic acid-leucine-arginine (ELR) tripeptide motif, which included interleukin-8 (IL-8), growth-regulated oncogene alpha (GROalpha), neutrophil-activating peptide-2 (NAP-2), and epithelial cell-derived neutrophil activating peptide-78 (ENA-78), induced calcium flux in the cells. These observations suggested that the receptor CXCR2 (IL-8RB) should be expressed on the surface of these cells. Using the RNAse protection assay, CXCR2 mRNA, but not CXCR1 (IL-8RA) mRNA expression was detected in HMC-1 cells. Flow cytometry analysis documented the surface expression of CXCR2. A binding analysis performed with 125I-IL-8 determined that there were approximately 3,600 high affinity IL-8 binding sites per HMC-1 cell, with a calculated kd of 1.2 to 2 nmol/L. The activity of this receptor was further explored using IL-8, which was found to induce dose-dependent chemotactic and haptotactic responses in both HMC-1 cells and in vitro cultured human cord blood-derived mast cells. These results show the expression of functional CXCR2 receptors on the surface of human mast cells, which may play an important role in mast cell recruitment during the genesis of an inflammatory response.

Amino Acid Sequence↗
PubMed1999

Regulatory role of mevalonate and N-linked glycosylation in proliferation and expression of the EWS/FLI-1 fusion protein in Ewing's sarcoma cells.

The Ewing's sarcoma cell line RD-ES, which carries the EWS/FLI-1 fusion gene, responded to the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin with growth arrest. Replenishment of mevalonate (MVA) to the arrested cells restored cell growth. However, if tunicamycin (TM), which is an inhibitor of N-linked glycosylation, was present together with MVA the cells remained arrested, indicating that N-linked glycosylation is of importance for growth of Ewing's sarcoma cells. Inhibition of the biosynthesis of EWS/FLI-1 fusion protein by treatment with antisense oligonucleotides also led to growth arrest, suggesting that this protein is of importance for cell growth. We investigated whether MVA synthesis and N-linked glycosylation could be involved in regulation of the expression of the EWS/FLI-1 fusion protein, which in fact contains four potential sites for N-linked glycosylation. We found that inhibition of both HMG-CoA reductase and N-linked glycosylation drastically decreased the expression of the fusion protein, which mainly appears in the cell nuclei. There was no significant difference in the inhibitory effect on the fusion protein between the cytoplasm and the cell nuclei, indicating that the transport of the fusion protein to the cell nucleus is not affected. The fusion protein did not exhibit any gel electrophoretic mobility shift after treatment of the cells with lovastatin or TM, and it did not incorporate [3H]glucosamine. Therefore we can conclude that the fusion protein is not a glycoprotein. The decreased expression of the fusion protein following lovastatin or TM treatment was found to be due to a lowered stability of de novo-synthesized fusion protein. The down-regulation of the fusion protein was correlated to growth arrest. Furthermore, the kinetics between the expression of EWS/FLI-1 fusion protein and the initiation of DNA synthesis in MVA-stimulated cells were similar. Taken together, our data suggest that the regulatory role of N-linked glycosylation in the expression of the EWS/FLI-1 fusion protein is important for growth of Ewing's sarcoma cells. Possible mechanisms underlying TM-induced decrease in EWS/FLI-1 expression may involve the breaking of growth factor receptor pathways.

Amino Acid Sequence↗
PubMed1999

Serum amyloid A induces chemotaxis of human mast cells by activating a pertussis toxin-sensitive signal transduction pathway.

Serum amyloid A (SAA) is an acute-phase protein and its concentration increases in the blood up to 1000 times during an inflammatory response. Mast cells are known to accumulate in various inflammatory processes, some of which are associated with increased levels of acute-phase reactants such as SAA. We report here that SAA can act as a mast cell chemoattractant. Recombinant SAA at concentrations corresponding to those found during the acute phase induced directional migration of human mast cells. No chemokinetic effect was observed. Preincubation of the cells with pertussis toxin inhibited SAA chemotaxis, suggesting that the effect is mediated by G proteins of the Gi class. Furthermore, chemotaxis was diminished after pretreatment with genistein, a tyrosine kinase inhibitor, or bisindolylmaleimide I, a protein kinase C inhibitor. We suggest that SAA may participate in the migration of mast cells to inflamed tissues during an acute-phase response, acting through a pertussis toxin-sensitive signaling pathway.

Cell Line↗
PubMed1999

Red blood cell velocity and volumetric flow assessment by enhanced high-resolution laser Doppler imaging in separate vessels of the hamster cheek pouch microcirculation.

An enhanced high-resolution laser Doppler imager (EHR-LDI), configured to fit the demands of a measurement area containing separate microvessels, was evaluated for perfusion measurements in hamster cheek pouch preparations during ischemia, reperfusion, and pharmacologically induced vasodilation and vasoconstriction. Measurements in separate microvessels where the laser beam was smaller than the vessel diameter were referred to as red blood cell (RBC) velocity estimates, as previously validated in vitro, whereas a relative flow index, RFI (mean RBC velocity/tissue area), was introduced as a volumetric flow measure. Microvessel diameter and RBC velocity changes during ischemia, reperfusion, as well as during vasoconstriction and vasodilation correlated to the data obtained from the microscope. Correspondingly, during the described provocations anticipated volumetric flow changes were registered as changes in the RFI. When data on intravessel RBC velocity profiles are presented they reflect a parabolic flow profile usually seen in this size microvessel. The EHR-LDI appears a promising tool for investigation of the microvasculature, as it almost simultaneously provides information on relative changes of both in vivo RBC velocity and volumetric flow (RFI), although the latter estimate needs to be further refined.

Adenosine↗
PubMed1999

An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F).

Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.

Adolescent↗
PubMed1999

Ki-67 is strongly prognostic in synovial sarcoma: analysis based on 86 patients from the Scandinavian Sarcoma group register.

In a study based on formalin-fixed paraffin-embedded material from 86 patients with primary synovial sarcoma located in the extremities or on the trunk wall, the prognostic importance of MIB-1 index, p53-expession and tumour size was analysed. Multivariate analysis identified two metastatic risk factors: increasing tumour size and MIB-1 > 9%. The 5-year metastasis-free survival-rate for patients with tumour size < or = 5 cm + MIB-1 < 10% was 0.83 (95% confidence interval (CI) 0.64-0.92) compared to 0.31 (95% CI 0.11-0.53) in cases with tumour size > 5 cm + MIB-1 > or = 10%. Our study shows that metastatic disease in synovial sarcoma is closely related to MIB-1 index. Using our model based on tumour size and MIB-1 index, cases with good and poor prognosis can easily be discriminated. Therefore our model can be used to identify patients who should be considered for adjuvant chemotherapy.

Antigens, Nuclear↗
PubMed1999

The potential of human mast cell progenitors to differentiate into mature mast cells remains after prolonged culture with flt3 ligand, interleukin-3 or granulocyte-macrophage colony stimulating factor.

Stem cell factor (SCF) plays a key role in the development of mast cells from haemopoietic progenitor cells. In this study we have investigated the effect of the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By using delayed addition of SCF, we examined the potential of mast cell progenitors to keep their capacity to differentiate into mast cells after exposure to factors signalling differentiation into other lineages. Culture with either cytokine for 3 weeks before transfer to SCF-containing medium resulted in the development of mast cells in all cultures. The appearance of mast cells was attenuated when the cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells had not lost the capacity to develop into mast cells. In contrast, in cultures initiated with FL and transferred to medium containing SCF, the same amount of mast cells developed as in the SCF cultures. Thus, cells committed to the mast cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF and keep their potential to differentiate into mature mast cells.

Adjuvants, Immunologic↗
PubMed1999

Skeletal muscle blood flow after prolonged tourniquet ischaemia and reperfusion with and without intervening reoxygenation: an experimental study in rats using laser Doppler perfusion imaging.

The total, safe, time available for operating during tourniquet ischaemia is thought to be prolonged by short, intervening episodes of reperfusion. However, animal experiments have suggested that this may cause a reduction of the postischaemic reperfusion injury. The purpose of the present study was to investigate the effect on final postischaemic reperfusion of intermittent, short periods of reperfusion compared with that of prolonged, continuous tourniquet ischaemia. A rat tourniquet model of total limb ischaemia and laser Doppler imaging to measure postischaemic microvascular perfusion in skeletal muscle was used in a total of 25 anaesthetised rats. Four were non-ischaemic controls. In 21 rats one hind leg was made totally ischaemic by a tourniquet. Fourteen were exposed to uninterrupted periods of either 1.5 hours or three hours, and seven to interrupted total ischaemia of three hours, with a 20 minutes reperfusion interval after 1.5 hours of ischaemia. The postischaemic blood flow was monitored 20 minutes after release of the tourniquet. Postischaemic skeletal muscle blood flow was significantly reduced after three hours of continuous ischaemia compared with the group that had an intervening short period of reoxygenation. The postischaemic reperfusion after three hours of ischaemia with a short reperfusion interval was not reduced after ischaemia compared with either that in controls or to that in the group exposed to only 1.5 hours of tourniquet ischaemia. These findings support the clinical practice of using intervening periods of reperfusion to prolong the total tourniquet time that can safely be used. There were no adverse effects on postischaemic reperfusion from intermittent reoxygenation.

Animals↗
PubMed1999

Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.

In this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway.

Blotting, Western↗
PubMed1999

Effects of intramuscular omeprazole on gastric acid secretion in horses over a twenty-four hour period.

The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was 2.1-4.2 and after omeprazole treatment, pH 2.8-4.1 (LD) and 2.4-6.6 (HD). After stimulation, the corresponding pH values were 2.6-3.3, 3.9-4.9 and 5.4-7.2. The biological availability of omeprazole was 70-80%. Due to the simplicity of the administration technique and the higher biological availability, intramuscular administration may offer a practical and less expensive way of treating gastric ulcers in horses.

Animals↗
PubMed1999

Post-mortem findings of gastric ulcers in Swedish horses up to one year of age: a retrospective study 1924-1996.

Necropsy records from 702 horses, less than one year old, that were subjected to necropsy between 1924 and 1996 were used to estimate the prevalence of gastric ulceration in younger horses and to evaluate some potential risk factors that may contribute to the development of gastric ulceration. Information concerning breed, gender, age, season of death, clinical signs of colic, medical treatment, parasitism and documentation of diseases in different organs were recorded, as well as size, number and anatomical distribution of ulcers. Gastric ulcers were found in 96 of 702 young horses (14%) and gastritis in another 64 animals (9%). The cutaneous region adjacent to margo plicatus (51%), and the corpus region were commonly affected (46%). The investigation clearly demonstrates that gastric ulceration has affected young Swedish horses to a similar degree during most of the 20th century. A significant (p < or = 0.05) association between gastric ulcers and the signs of colic, parasitism and a concomitant intestinal, liver, and oesophageal involvement was found. No breed or sex predilection with gastric ulcers was obtained. The risk of gastric ulcers was highest during the fall (odds ratio 3.52) and lowest during the summer (odds ratio 0.45). The seasonal variation could not be explained by concomitant findings of Gasterophilus larvae. By using a multivariate logistic regression analysis, only season significantly influenced the risk of gastric ulceration.

Aging↗