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Biomedical subjects

G Nilsson

Publications and source records attributed to G Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed2002

The prognostic value of global haemostatic tests in the intensive care unit setting.

BACKGROUND: Global haemostatic tests are often abnormal in critically ill patients, secondary to activation or consumption of coagulation factors or inhibitors. Methods for analysing plasma levels of these factors are, however, not widely available, and the predictive value of global tests is not known. We examined the clinical applicability to predict the outcome of the global haemostatic tests used at most hospitals. METHODS: Blood was collected from patients within 6 h of admission to an intensive care unit (ICU) and tested regarding platelet count, International Normalized Ratio (INR), and activated partial thromboplastin time (APTT). Ninety-two patients with platelet counts <100 x 10(9) l(-1), INR > 1.36 and/or APTT >45 s were included in a study group, and an additional 92 patients with a comparable age and sex distribution, but not fulfilling these laboratory criteria, constituted a control group. The following data were recorded for each patient: number of days in the ICU and hospital; alive or deceased when released from the ICU and hospital; survival at 30 days and 180 days. RESULTS: Survival upon discharge from the ICU and hospital was significantly reduced in the study group. This was especially pronounced in patients with medical disorders, whereas the survival rate was slightly higher in surgery patients. Expressing the survival predicting ability of the screening tests as odds ratios for all patients (study and control groups together) indicated that prolonged APTT in particular foretold a lower survival rate at studied time-points after admission to the ICU. CONCLUSIONS: The global haemostatic tests INR and APTT can predict survival in critically ill patients, and prolonged APTT in particular seems to be associated with a negative prognosis.

Aged↗
PubMed2002

Randomized clinical trial of laparoscopic versus open fundoplication: evaluation of psychological well-being and changes in everyday life from a patient perspective.

BACKGROUND: The laparoscopic approach in antireflux surgery might have an impact on the patient's daily activities and well-being. METHODS: Sixty patients were randomized to laparoscopic or open 360 degrees fundoplication. Data were collected by questionnaires and interviews preoperatively, 1 month and 6 months after operation. RESULTS: Five patients in the laparoscopic group were converted to open surgery. Psychological general well-being increased after surgery and reached norm values in both study groups. No significant differences were found between the two types of surgery in the per protocol analysis, while the domain self-control was significantly better after open surgery in the intention-to-treat analysis. There was improvement of diet and sleep in both study groups; after 6 months, disturbed sleep was significantly more uncommon after open surgery. Dysphagia and flatulence were new symptoms that were reported after surgery. Overall perception of the results of the operation did not differ between the groups. CONCLUSIONS: Psychological general well-being, diet and sleep improved after both laparoscopic and open surgery. There were only small differences between the groups, but in some respects the results were better after open surgery.

Adult↗
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

[How to manage all those ECGs? Experiences with computer-based storage and interpretation of electrocardiograms in the county of Vastmanland].

We describe our experience using a database (Sicare, Siemens Elema) containing 381,000 ECGs covering 90% of all ECGs during 11 years in the county of Västmanland, Sweden, with 260,000 inhabitants. The database expedites rapid recovery of earlier ECGs. For instance, in patients admitted to coronary care with chest pain and ST-elevation, speedy access to an earlier ECG with identical ST-elevation may be crucial for avoiding unnecessary and potentially harmful thrombolysis. The database also enables us to select ECGs with a specific diagnosis, for instance atrial fibrillation. This facilitates characterization and quality control of treatment of atrial fibrillation in a well-defined population.

Archives↗
PubMed2001

The Kit-activating mutation D816V enhances stem cell factor--dependent chemotaxis.

The D816V mutation of c-kit has been detected in patients with mastocytosis. This mutation leads to constitutive tyrosine kinase activation of Kit. Because stem cell factor (SCF), the ligand for Kit (CD117(+)), is a chemoattractant for CD117(+) cells and one feature of mastocytosis is an abnormal collection of mast cells in tissues derived from CD34(+)CD117(+) mast cell precursors, the hypothesis was considered that the D816V mutation would enhance chemotaxis of these precursor cells. Constructs encoding wild-type Kit or Kit bearing the D816V mutation were transfected into Jurkat cells, labeled with Calcein-AM, and migration to SCF assessed in the presence or absence of tyrosine kinase inhibitors. Chemotaxis to SCF was enhanced in D816V transfectants compared to wild-type Kit transfectants (P <.002). Migration of both transfectants was inhibited by tyrosine kinase inhibitors, although D816V transfectants were more sensitive. Chemotaxis was next performed on CD34(+)CD117(+) circulating mast cell precursors obtained from patients with mastocytosis. Analysis of prechemotaxis and migrated cells showed that whereas less than 10% in the prechemotaxis sample had the D816V mutation, 40% to 80% of migrated cells had this mutation. These results demonstrate that the D816V Kit mutation enhances chemotaxis of CD117(+) cells, offering one explanation for increased mast cells observed in tissues of patients with mastocytosis. (Blood. 2001;98:1195-1199)

Antigens, CD34↗
PubMed2001

Retention behaviour of amylopectins in asymmetrical flow field-flow fractionation studied by multi-angle light scattering detection.

Asymmetrical flow field-flow fractionation (FFF) with multi-angle light scattering (MALS) detection was applied for the fractionation of amylopectins from four different sources. Samples originated from genetically modified potatoes and waxy maize. Amylopectins were dissolved in a 1 mol l(-1) sodium hydroxide solution or water. With an injected mass of 0.2 microg, well below overloading conditions, a decrease of the apparent hydrodynamic radius with increasing inlet flow-rate was observed. Moreover, a decrease of the radius of gyration with increasing elution volume was recorded by the MALS detector. Steric/hyperlayer effects are a feasible explanation for this behaviour. The observed radius of gyration at the steric inversion point was in the order of 0.3 microm, which is smaller than the theoretically calculated inversion point. Apparently, the amylopectin behave as macromolecules with a larger hydrodynamic radius than expected on basis of their radius of gyration and are subjected to significant lift forces. The results were confirmed by four fractionations with varying flow-rates but constant ratio of cross to outlet-flow. In contrast to the normal mode operation, the retention of the amylopectins depended strongly on the applied flow-rates and was close to that of a much smaller 10 kDa dextran. Apparent molar masses in the order of between 10(7) and 10(9) g mol(-1) were obtained. The results are contrasted with enzymatically degraded and oxidised starch samples that were fractionated in the normal mode.

Amylopectin↗
PubMed2001

Stem cell factor-induced migration of mast cells requires p38 mitogen-activated protein kinase activity.

Stem cell factor (SCF) can be considered a cardinal cytokine in mast cell biology as it affects mast cell differentiation, survival, and migration. The objective of this study was to investigate the role of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, in SCF-induced cell migration. This was examined in mouse mast cells by using PD 098059 and SB203580, which are specific inhibitors of mitogen-induced extracellular kinase (MEK) and p38 MAP kinase, respectively. SCF induced a rapid and transient activation of ERK and p38 in a dose-dependent manner. Inhibition of p38 activity by SB203580 was paralleled with a marked reduction of migration toward SCF, whereas the effect of the MEK inhibitor was less pronounced. This is the first report of a physiological function of SCF-dependent activation of p38. Whether p38-mediated mast cell migration is a possible target for suppression of mast cell hyperplasia remains to be determined.

Animals↗
PubMed2001

Distinct and regulated expression of Notch receptors in hematopoietic lineages and during myeloid differentiation.

Hematopoietic development is a delicate balance of cell fate decisions in multipotent cells between self-renewal and differentiation. In multiple developmental systems, the Notch receptors are important factors regulating these processes. Hematopoietic progenitor cells have been shown to express Notch1, and studies with an activated intracellular form has revealed a functional role. To assess the function of other Notch members in hematopoiesis, we investigated the expression pattern of Notch1, Notch2, and Notch3 in hematopoietic lineages at the level of RNA and protein. We demonstrate that Notch1 and Notch2 are expressed in multiple lineages, and that Notch1 in particular appears to be regulated during myeloid differentiation. Notch1 was up-regulated and expressed at high levels in adherent macrophages. Mast cells expressed only low levels of Notch1 mRNA whereas Notch2 mRNA was highly expressed. In addition we could detect Notch3 mRNA and protein in cell lines representing mast cell progenitors. These expression patterns imply that the different Notch genes may have very distinct functions during hematopoiesis, and that Notch3 could be a specific regulator of mast cell development. The finding that Notch1 was up-regulated in the adherent cells developing from a multipotent progenitor cell line suggests that this protein may posses dual functions in hematopoiesis, i.e. at the stage of cell fate decision, and at the maturation stage of monocytes when adhesion to the specific microenvironment is accomplished.

Animals↗
PubMed2001

Short-term outcome after laparoscopic and open 360 degrees fundoplication. A prospective randomized trial.

BACKGROUND: Despite the lack of randomized trials supporting the laparoscopic approach, laparoscopic antireflux surgery has gained widespread acceptance during the last decade. The aim of this study was to compare the short-term symptomatic and objective outcome after laparoscopic and open 360 degrees fundoplication in a prospective randomized clinical trial. METHODS: Sixty patients with GERD were randomized to undergo either laparoscopic (LF) or open 360 degrees fundoplication (OF). Endoscopy, esophageal manometry, 24-h pH monitoring, clinical symptom evaluation, and symptom scoring according to a validated questionnaire (the Gastrointestinal Symptom Rating Scale [GSRS]) was performed preoperatively and 6 months after surgery. RESULTS: Five patients randomized to the laparoscopic group were converted to open surgery. Esophageal acid exposure was restored to normal in all patients. Lower esophageal sphincter length and resting pressure were significantly increased after both laparoscopic and open fundoplication (p < 0.001); there were no differences between the groups. No significant differences were seen in symptomatic outcome, although there was a trend toward a higher rate of mild dysphagia (p = 0.051) after laparoscopic surgery. GSRS revealed a decrease in reflux score (p < 0.001) and abdominal pain score (p < 0.001) postoperatively. There were no significant differences in GSRS scores between the two groups. CONCLUSION: Laparoscopic 360 degrees fundoplication is as effective in treating reflux disease as open fundoplication. Six months postoperatively, no significant differences were seen in symptomatic or objective outcome. Long-term evaluation is needed.

Adult↗
PubMed2001

Transforming growth factor-beta-mediated mast cell migration depends on mitogen-activated protein kinase activity.

Transforming growth factor-beta (TGF-beta) isoforms regulate numerous cellular functions through binding to receptors with intrinsic serine/threonine kinase activity that transduce the intracellular signals via activation of Smad proteins. In this study, we examined the signalling pathways involved in TGF-beta1-mediated growth inhibition and migration in a human mast cell line, HMC-1. TGF-beta1 evoked optimal migration at 40 fM, whereas maximal growth inhibition was obtained at 400 pM. Protein tyrosine kinase inhibitors completely inhibited TGF-beta1-mediated migration, without affecting the antimitogenic response. Smad2 was phosphorylated upon TGF-beta1 treatment, both in the absence and presence of genistein. The mitogen-induced extracellular kinase (MEK) inhibitor, PD98059, blocked the migratory response without affecting growth inhibition. In contrast, the p38 MAP kinase inhibitor, SB203580, had no significant effect on either migration or growth inhibition. These results indicate that different signalling pathways mediate TGF-beta1-induced migration and growth inhibition in HMC-1 cells, where the migration involves MEK activity.

Cell Division↗
PubMed2001

Inhibition of keratinocyte growth in cell culture and whole skin culture by mast cell mediators.

Mast cells are suggested to participate in regenerative processes, but their influence on epithelialization and wound healing has not been well studied. Since mast cells can be found in contact with epidermis in chronic inflammatory skin diseases and venous ulcers, the effect of mast cells on keratinocyte growth was studied. Keratinocytes were cultured in serum-free conditions with (complete medium) or without (basal medium) epidermal growth factor (EGF) and bovine pituitary extract (BPE) to reach subconfluence in a 24-well plate, and the cells were treated with different mast cell mediators histamine, heparin and tryptase, or lysate from HMC-1 cells, a human leukemic mast cell line. Whole skin cultures were used as a model for in vitro wounds to study the effect of mast cells on epithelial outgrowth from skin specimens. Histamine inhibited 3H-thymidine incorporation of keratinocytes dose-dependently by 29% at 1 mM, and 89% at 5 mM histamine. In whole skin culture, histamine inhibited epithelial outgrowth dose-dependently by 64% already at 0.1 mM histamine and maximally (91%) at 1 mM histamine. Heparin inhibited 3H-thymidine incorporation dose-dependently by up to 33% at 2 microg/ml in the absence, but not in the presence, of EGF/BPE. In contrast, in whole skin culture, heparin first inhibited the epithelial outgrowth by up to 27% at 2 microg/ml, but then reversed the inhibition to 30% stimulation at 200 microg/ml. Skin tryptase (0.0285 to 2.85 microg/ml) with or without heparin (0.5 to 20 microg/ml) did not affect thymidine incorporation in keratinocytes. Lysate from HMC-1 cells, but not that from control, neuroblastoma cells, inhibited 3H-thymidine incorporation in keratinocytes dose-dependently, and maximal (47%) inhibition was reached with 16,700 lysed HMC-1 cells/ml. In whole skin culture, HMC-1 lysate inhibited the epithelial outgrowth by up to 36% at 67,000 lysed cells/ml. The results show that mast cells and their mediators are inhibitory to keratinocyte 3H-thymidine incorporation and epithelial outgrowth in vitro, although, the inhibitory effect of histamine was seen at high concentrations suggesting a requirement for close morphologic vicinity of mast cells to keratinocytes. Thus, mast cells are assumed to control epidermal regeneration and to impair epithelialization of chronic ulcers.

Cell Division↗
PubMed2001

Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease.

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Adult↗
PubMed2001

Left ventricular systolic dysfunction in 75-year-old men and women; a population-based study.

AIMS: To determine the prevalence of left ventricular systolic dysfunction in 75-year-old men and women. METHODS AND RESULTS: In a population-based random sample of 75-year-old subjects (n=433; response rate 70.1%) the left ventricular systolic function was determined using two echocardiographic methods: (1) wall motion in nine left ventricular segments was visually scored and wall motion index was calculated as the mean value of the nine segments and (2) ejection fraction as measured by the disc summation method. Presence of heart failure was determined by a cardiologist's clinical evaluation. Wall motion index was achievable in 95% of the participants while ejection fraction was measurable in 65%. Normal values were obtained from a healthy subgroup (n=108) and left ventricular systolic dysfunction was defined as the 0.5th percentile of the wall motion index (i.e. <1.7). In participants in whom both ejection fraction and wall motion index were achievable, wall motion index <1.7 predicted ejection fraction <43% with a sensitivity and specificity of 84.0% and 99.6%, respectively. The prevalence of left ventricular systolic dysfunction was 6.8% (95% CI, 5.6--8.0%) and was greater in men than in women (10.2% vs 3.4%, P=0.006). Clinical evidence of heart failure was absent in 46% of the participants with left ventricular systolic dysfunction. CONCLUSIONS: Left ventricular systolic dysfunction is common among 75-year-olds with a prevalence of 6.8% in our estimate. The condition is more likely to affect men than women. In nearly half of 75-year-olds with left ventricular systolic dysfunction there is no clinical evidence of heart failure.

Age Distribution↗
PubMed2001

Myocardial infarction and prevalence of diabetes mellitus. Is increased casual blood glucose at admission a reliable criterion for the diagnosis of diabetes?

AIMS: To investigate the prevalence of diabetes mellitus in patients with acute myocardial infarction and to determine whether casual blood glucose and haemoglobin A1c measured at admission could be used to diagnose diabetes mellitus. METHODS AND RESULTS: A prospective study that included all patients with acute myocardial infarction hospitalized during a one-year period at a coronary care unit. Casual blood glucose was measured at admission, fasting blood glucose during the hospital stay and, if necessary for classification, 2-3 months after discharge. Haemoglobin A1c was measured once at admission. Of 305 patients included in the study, 285 could be classified into three groups: 21% of these had previously diagnosed diabetes, 4% had newly diagnosed diabetes and the remaining patients were categorized as non-diabetic. Casual blood glucose >or=11.1 mmol x l(-1)at admission was found in 12 patients with no previously known diabetes, but diabetes mellitus was confirmed in only six of these patients. Haemoglobin A1c showed considerable overlapping of values between the three groups of patients (i.e. patients with known diabetes mellitus, patients with newly diagnosed diabetes mellitus and non-diabetics). CONCLUSION: One of four patients with acute myocardial infarction had diabetes mellitus. Increased casual blood glucose at admission was not a reliable measure to establish a diagnosis of diabetes and thus follow-up measures were necessary. Haemoglobin A1c was found to be an unreliable measure in the verification of diabetes.

Aged↗
PubMed2001

IgE-mediated mast cell degranulation and recovery monitored by time-lapse photography.

BACKGROUND: Mast cells are long-lived resident cells that are of great importance in an allergic reaction. It has previously been suggested that after IgE-mediated degranulation mast cells can undergo regranulation. Such a process is probably of great importance with respect to the severity and perpetuation of the allergic response. OBJECTIVE: Our purpose was to investigate whether mast cells recover from degranulation and whether they still have the potential to release a granule-associated mediator and upregulate certain cytokine genes. METHODS: Mouse mast cells were repeatedly activated by IgE and specific antigen with a 24-hour or 48-hour interval. During each of the 2 activation stages, release of beta-hexosaminidase was measured by means of enzymatic colorimetric analysis, and IL-13 and IL-6 mRNA was detected by ribonuclease protection assay. Both scanning electron microscopy and time-lapse photography were used to reveal the process of mast cell recovery. RESULTS: We found that re-activation of degranulated mast cells in response to high-affinity IgE-receptor cross-linkage triggers beta-hexosaminidase release and upregulation of IL-13 and IL-6 gene expression levels similar to what is seen in the initial activation. Scanning electron microscopy documented cells at various stages during the recovery process 30 minutes after the activation. With time-lapse photography, a single cell that had undergone degranulation could be visualized consecutively during its recovery process. CONCLUSION: Mast cells can recover after an IgE-mediated activation and can repeatedly release beta-hexosaminidase and express IL-6 and IL-13 mRNA after re-activation.

Animals↗
PubMed2001

Demonstration of mast cell chemotactic activity in synovial fluid from rheumatoid patients.

OBJECTIVES: The significance of the mast cell in the pathogenesis of rheumatic diseases has become more evident. Although mast cell hyperplasia is a feature of rheumatoid arthritis, the nature of mast cell chemoattractants involved in the recruitment of mast cells in joint diseases has not been studied in any detail. In this study the presence of mast cell chemotactic activity in synovial fluids was examined. METHODS: Synovial fluids from seven rheumatoid patients were tested in a modified Boyden chamber, where a human mast cell line was used as responder. The presence of stem cell factor (SCF) and transforming growth factor beta (TGFbeta) was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Six of the seven synovial fluids tested exhibited mast cell chemotactic activity. Two characterised human mast cell chemotaxins, SCF and TGFbeta, were highly expressed in the synovium. Soluble SCF could be detected in all fluids analysed. Blocking antibodies against SCF or TGFbeta almost completely blocked the activity in one fluid, partially blocked the activity in three, and did not affect the activity in two. Treatment of the responder cells with pertussis toxin reduced the migratory response against seven fluids, indicating the presence of chemoattractants mediating their effect through G(i) coupled receptors. CONCLUSION: These data demonstrate the presence of multiple factors in synovial fluid acting as mast cell chemoattractants, two of which are SCF and TGFbeta that contribute to the effect. These findings may be of importance for developing new strategies to inhibit mast cell accumulation in rheumatic diseases.

Adult↗