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P Andersson

Publications and source records attributed to P Andersson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alpha-1-antitrypsin is present in the specific granules of human eosinophilic granulocytes.

Eosinophils may be found at sites of inflammation, for example in asthma, allergy and helminthic infestation, but their role in human inflammatory disease is unclear. In the present study, we investigated the presence of alpha-1-antitrypsin (AAT), a serine proteinase inhibitor, in human eosinophils. When lysates of highly purified eosinophils were subjected to Western blotting, with a chemiluminescent substrate, immunoreactive bands were seen. An ELISA was developed to measure the AAT content, which was found to be about 100 ng/5 x 106 eosinophils, about 50 ng/5 x 106 neutrophils, and about 25 ng/5 x 106 monocytes. Immunoelectron microscopy showed localization of AAT to the specific granules of eosinophils. During prolonged incubation of eosinophils, no significant increase in the total amount of AAT could be detected by ELISA. However, there was an increased level of AAT in the medium, in parallel with a decrease in the intracellular AAT content, suggesting release of preformed AAT. Apparent complex formation between iodinated elastase and AAT in eosinophil lysates provided evidence that the AAT is functionally active. On the basis of these findings it is suggested that by releasing AAT, eosinophils may, in a microenvironment, play a role in counteracting the tissue damage caused by serine proteinases released by neutrophils in inflammatory conditions.

Cytoplasmic Granules↗
PubMed2001

Eating difficulties, need for assisted eating, nutritional status and pressure ulcers in patients admitted for stroke rehabilitation.

The aim of this study was to describe the types and extent of eating difficulties, the need for assistance when eating, the nutritional status and pressure ulcers in consecutive patients (n = 162) admitted for stroke rehabilitation over a period of 1 year. Structured observations and assessments of eating, nutritional status (subjective global assessment of nutritional status), pressure ulcers and activities in daily living (Katz ADL-index) were performed by a nurse who also trained the staff to perform these assessments. Difficulties in eating were found in 80%, and 52.5% were unable to eat without assistance. Eating difficulties were: 'eats three-quarters or less of served food' (60%), difficulties in 'manipulating food on the plate' (56%), 'transportation of food to the mouth' (46%), 'sitting position' (29%), 'aberrant eating speed' (slow or forced) (26%), 'manipulating food in the mouth' (leakage, hoarding, chewing difficulties) (24%), 'swallowing difficulties' (18%), 'opening and/or closing the mouth' (16%), and 'alertness' (9%). Thirty-two percent were undernourished (49% of patients needing assisted eating and 13% of those not needing assistance, P < 0.0005). Among patients who were dependent in one or more functions according to the Katz ADL-index, 15% had pressure ulcers. The strongest eating variables for predicting nutritional status were 'alertness', 'swallowing difficulties', 'eats three-quarters or less of served food', and 'aberrant eating speed'. Nutritional status could in turn significantly predict pressure ulcers. Eating difficulties among patients with stroke are complex and the patient's situation before stroke adds to this complexity, especially among those dependent on assisted eating. As difficulties occur both among patients needing and not needing assisted eating, all patients with stroke admitted for rehabilitation need to be systematically assessed for eating difficulties and action needs to be taken to facilitate eating, especially as patients with eating difficulties risk becoming undernourished and in turn developing pressure ulcers.

Activities of Daily Living↗
PubMed2001

Bactericidal activity of human eosinophilic granulocytes against Escherichia coli.

Eosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production L-N(5)-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells.

Aerobiosis↗
PubMed2001

Men of low socio-economic and educational level possess pronounced deficient knowledge about the risk factors related to coronary heart disease.

BACKGROUND: The aim of the present study was to determine whether certain background factors such as gender, education and social status were associated with an individual's knowledge of coronary heart disease (CHD) risk factors. DESIGN: A questionnaire survey. METHODS: A questionnaire survey designed to evaluate participants' general knowledge about the risk factors for CHD was used. A total of 1011 50-year-old individuals (457 men and 554 women) from 34 Health Care Centers participated in the study. RESULTS: Knowledge about CHD risk factors was significantly poorer in men than in women. Low education and low socio-economic status were other factors related to poor knowledge of CHD risk factors. CONCLUSION: This study showed that men with low educational level and low socio-economic status had inadequate information about the risk factors involved in CHD.

Coronary Disease↗
PubMed2001

P1198: software for tracing decision behavior in lending to small businesses.

This paper describes a process-tracing software program specially designed to capture decision behavior in lending to small businesses. The source code was written in Lotus Notes. The software runs in a Web browser and consists of two interacting systems: a database and a user interface. The database includes three realistic loan applications. The user interface consists of different but interacting screens that enable the participant to operate the software. Log files register the decision behavior of the participant. An empirical example is presented in order to show the software's potential in providing insights into judgment and decision making. The implications of the software are discussed.

Accounting↗
PubMed2000

Computational predictions of binding affinities to dihydrofolate reductase: synthesis and biological evaluation of methotrexate analogues.

The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.

Animals↗
PubMed2000

A phase I trial of solubilized DR2:MBP84-102 (AG284) in multiple sclerosis.

OBJECTIVE: To assess the safety, tolerability, and biologic and clinical activity of a solubilized complex comprised of human leukocyte antigen-DR2 with myelin basic protein84-102 (AG284)in patients with secondary progressive MS. BACKGROUND: Soluble species-specific major histocompatibility complex myelin basic protein91-103 complexes ameliorate disease in a dose-dependent manner when administered to SJL/J mice with chronic relapsing experimental allergic encephalomyelitis. Preincubation with AG284 reduces the proliferative response of a DR2-restricted, myelin basic protein84-102-reactive T cell clone, derived from a MS patient, to myelin basic protein84-102 in the presence of autologous antigen-presenting cells. METHODS: Thirty-three patients with secondary progressive MS were randomly assigned to receive three alternate day IV doses of AG284 or placebo in a double-masked dose escalation study. The primary outcome was safety and tolerability. Secondary outcomes included a comparison of pre- and post-treatment gadolinium-enhanced brain MRI activity, Kurtzke Expanded Disability Status Scale, and Nine Hole Peg Test scores. RESULTS: The frequency of adverse events was similar in the AG284 and placebo recipients. No significant treatment effect was detected by Expanded Disability Status Scale, Nine Hole Peg Test, or number of new gadolinium-enhancing MRI lesions. CONCLUSIONS: AG284 as administered during this study was safe and well tolerated. Further studies are warranted to determine the biologic activity and clinical efficacy of this potential treatment for MS.

Adult↗
PubMed2000

Time-shared X(omega(1))-half-filter for improved sensitivity in subspectral editing.

Experiments with X-half-filter elements allow the separation of the resonances from protons bound and unbound to a spin X into different subspectra. This Communication presents a modified half-filter element where the filter delay is simultaneously used for chemical shift labeling and scalar coupling evolution in a semi-constant time experiment. The filter element is demonstrated with a (1)H NOESY spectrum of a 28.5-kDa 2:1 complex between the uniformly (13)C-labeled N-terminal domain of Escherichia coli arginine repressor and operator DNA.

Carbon Isotopes↗
PubMed2000

Smoking, blood glucose control, and locus of control beliefs in people with type 1 diabetes mellitus.

The relations between blood glucose control (HbA(1c)), smoking, and health-related diabetes locus of control beliefs were studied in a consecutive adult sample of 187 patients with Type 1 diabetes who were free of diabetes complications. Those who were smokers (n=32) had poorer HbA(1c) values than non-smokers [7.5+/-1.4 (S.D.) vs 6. 8+/-1.2%, P=0.017]. When the patients were compared according to HbA(1c) quartiles, 17 of the smokers (53%) were found among those with worst blood glucose control. The smokers showed a lesser belief than the non-smokers in powerful others such as physicians and diabetes nurses in regards as diabetes control and the course of the disease [23.5+/-4.4 (S.D.) vs 25.8+/-5.5 (S.D.), P=0.05]. The group as a whole exhibited strong beliefs that their own behaviour was important for diabetes control. This belief appears incongruent with smoking behaviour. The results have implications for possible coping and defence strategies used by the smokers. Due to their worse blood glucose control, weaker beliefs in health care professionals, and possible denial-like coping strategies, smokers clearly need special attention in diabetes care, particularly in the view of their risk of developing long-term complications.

Adolescent↗
PubMed2000

Marked heterogeneity in protein levels and functional integrity of the thrombopoietin receptor c-mpl in polycythaemia vera.

Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an increased production of mature blood cells. The underlying pathogenic mechanisms behind PV are largely unknown. Thrombopoietin (TPO) is the most important cytokine for stimulation of megakaryocyte growth and formation of functional platelets. Recently, it has been shown that the receptor for TPO, c-mpl, is expressed on haematopoietic stem cells, and that TPO promotes the growth of these stem cells via binding to c-mpl. Quantitative or qualitative abnormalities of c-mpl function could thus theoretically play a role in the pathogenesis of different MPDs. Previous studies of the integrity of the c-mpl system in PV have produced conflicting results. We therefore studied c-mpl protein expression using immunoblot analysis in 15 PV patients and 10 healthy controls. Seven out of 15 PV patients (47%) exhibited similar c-mpl protein levels to the controls, whereas eight out of 15 patients (53%) showed either markedly reduced or absent levels of c-mpl. Five of the seven c-mpl-positive patients had only been treated by phlebotomy, whereas six out of eight c-mpl-negative patients were receiving treatment with hydroxyurea, anagrelide or alpha-interferon. Disease duration tended to be slightly longer in c-mpl-negative patients compared with c-mpl-positive patients (mean = 55 vs. 43 months). Tyrosine phosphorylation of JAK-2 in immunoprecipitates of platelets obtained after stimulation with TPO (100 and 1000 ng/ml) was normal in c-mpl-positive patients, whereas it could not be detected in c-mpl-negative patients. We therefore conclude that there exists a marked heterogeneity in c-mpl protein levels and functional integrity in PV. However, it seems less likely that c-mpl abnormalities per se are directly involved in the pathogenesis leading to the occurrence of PV, as c-mpl levels were similar to those seen in healthy individuals in about half of the patients under study.

Aged↗
PubMed1999

Characterization of a molten globule state of bovine carbonic anhydrase III: loss of asymmetrical environment of the aromatic residues has a profound effect on both the near- and far-UV CD spectrum.

Bovine muscle carbonic anhydrase (isoenzyme III; BCAIII) exhibited a three-state unfolding process at equilibrium upon denaturation in guanidine hydrochloride (GuHCl). The stable folding intermediate appeared to be of molten globule type. The stability towards GuHCl in terms of mid-point concentrations of denaturation were very similar for BCAIII and human CAII (HCAII). It was further demonstrated that the aromatic amino acid residues contributed significantly to the circular dichroism (CD) spectrum in the far-UV wavelength region during the native-->molten globule state transition. Thus, the ellipiticity change at 218 nm was shown to monitor the loss of tertiary interactions of aromatic side chains at the first unfolding transition as well as the rupture of secondary structure at the second unfolding transition. Similar aromatic contributions to the far-UV CD spectrum, but with varying magnitudes, were also noted for BCAII and HCAII, further emphasizing that interference of aromatic residues should not be neglected at wavelengths that normally are assigned to secondary structural changes.

Animals↗
PubMed1999

Capillary electrophoresis with end-capillary potentiometric detection using a copper electrode.

Potentiometric end-capillary detection in capillary electrophoresis has the advantage of relatively easy miniaturisation without having to compromise the concentration sensitivity. Potentiometric end-capillary detection using a copper electrode is also attractive because of the sensitive detection of many inorganic and organic UV-transparent ions and the ability to work in both direct and indirect mode. In this work, detection of a number of common anions in a tartrate electrolyte at pH 3 was studied. The influence of the end-capillary detection geometry on the detection performance was investigated. An end-capillary detection cell allowing the separation capillary to be changed without the need to realign the detection electrode was constructed and fitted into a commercial CE apparatus. Under the optimal configuration, which was a 25 microm diameter copper electrode aligned coaxially with a 25 microm capillary and positioned at a distance of about 25 microm from the capillary end, excellent peak shapes were achieved and comparison with simultaneous on-capillary photometric detection showed no additional peak broadening. Good sensitivity was obtained, resulting in concentration limits of detection (LODs) in the low microM range and mass LODs in the low amol range. Examples of separations of inorganic and organic anions are presented and the analytical potential of the detection method is assessed.

Copper↗
PubMed1999

Testing an oral assessment guide during chemotherapy treatment in a Swedish care setting: a pilot study.

Oral complications are common in patients with haematological malignancies who undergo chemotherapy treatment. A pilot study including 16 haematological patients was carried out to evaluate the oral status using an Oral Assessment Guide (OAG) and to test the reliability of the OAG. The oral assessments were made daily by registered nurses at a Department of Internal Medicine in Sweden. Once a week a dental hygienist made the oral assessments independent of the registered nurses in order to provide data for calculations of inter-rater reliability. All patients had varying degrees of alterations in the oral cavity, especially in the mucous membranes, teeth/dentures and gums. The inter-rater agreement between the nurses and the dental hygienist was good for saliva and swallow, and moderate for voice and gums. Assessments to detect alterations in the oral cavity afford the opportunity for early and individualized interventions and may decrease the risk of oral infections. It is necessary to train the nurses to ensure high levels of reliability in the oral assessments. The OAG seems to be a reliable and clinical useful tool for assessing the oral cavity status and determining changes.

Acute Disease↗
PubMed1999

Plasma thrombopoietin levels in liver cirrhosis and kidney failure.

BACKGROUND: Recently, c-Mpl ligand (thrombopoietin, TPO) has been cloned by several groups and found to be a primary regulator of thrombopoiesis. Its mRNA expression has been detected in several organs including kidneys, bone marrow stroma cells, muscles, and is very strongly expressed in the liver. OBJECTIVE: To clarify thrombopoiesis and the regulation of TPO in severe liver and renal failure. DESIGN: We analysed plasma TPO levels in patients with biopsy verified liver cirrhosis (n = 18; mean platelet count 115 +/- 54 x 109 L-1), in patients on chronic haemodialysis as a result of end-stage renal failure (n = 20; mean platelet count 295 +/- 94 x 109 L-1), and in healthy individuals (n = 20; mean platelet count 250 +/- 40 x 109 L-1). Plasma was prepared from EDTA-anticoagulated whole blood and a commercially available ELISA kit was used for the analysis. RESULTS: The mean plasma TPO concentration amongst the normal individuals was 50 +/- 14 pg mL-1. In the patients with liver cirrhosis and in patients on haemodialysis the mean TPO levels were 62 +/- 19 pg mL-1 and 46 +/- 17 pg mL-1, respectively. The mean plasma TPO concentration for the cirrhotic patients was significantly higher than the mean recorded for the healthy volunteers (P = 0.031), whereas no statistically significant differences in plasma TPO were seen between the group of end-stage renal failure and normals. CONCLUSION: Our results suggest that TPO production is maintained in liver cirrhosis and in renal failure, and that the thrombocytopenia in liver cirrhosis is not due to an impaired TPO production.

Adult↗
PubMed1999

Insulin-mediated vasodilation and glucose uptake are independently related to fasting serum nonesterified fatty acids in elderly men.

OBJECTIVES: To investigate candidate predictors for insulin sensitivity in healthy elderly males, with special reference to the influence of insulin-mediated skeletal muscle blood flow and serum nonesterified fatty acids (NEFA). SUBJECTS: From the participants in a health survey of 70-year-old males, focusing on cardiovascular risk factors, a subgroup of 46 men was sampled. Only men who declared themselves healthy and without medication were included. INTERVENTIONS: Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Leg blood flow was measured before and during the clamp, using the Doppler ultrasound technique. RESULTS: Hyperinsulinaemia [steady-state plasma insulin 105(15) mU L-1] increased leg blood flow by 10% (P < 0.004). When tested in bivariate analysis incremental leg blood flow was only significantly related to the serum NEFA concentration (r = - 0.38, P < 0.01) amongst a number of measured variables. Insulin-mediated glucose disposal was related to body mass index (BMI) (r = -0.49, P = 0. 0006), waist/hip ratio (r = - 0.31, P = 0.036), NEFA (r = - 0.50, P = 0.0004) and heart rate (r = - 0.34, P = 0.02). In multivariate analysis only BMI and NEFA remained significantly related to whole-body glucose uptake. CONCLUSIONS: The study demonstrates that in elderly men BMI and fasting serum NEFA but not insulin-induced vasodilation are related to insulin sensitivity. High fasting levels of NEFA relate to both impaired insulin-mediated vasodilation and impaired glucose disposal, respectively. These two insulin actions were not interrelated, however, a finding which may indicate dissociated mechanisms.

Aged↗
PubMed1999

Do ACE-inhibitors suppress tumour necrosis factor-alpha production in advanced chronic renal failure?

OBJECTIVES: The serum levels of the catabolic cytokine TNF-alpha are often raised in malnourished chronic heart failure patients as well as in chronic renal failure (CRF) patients. Angiotensin-converting enzyme (ACE) inhibitors are often used in these patients and may decrease TNF-alpha and IL-1beta levels in vitro and in vivo. The aim of this study was to find out whether CRF patients with ongoing ACE-inhibitor treatment have lower TNF-alpha levels. DESIGN: Cross-sectional study. SETTING: Tertiary Referral Center and University Hospital. SUBJECTS: Ninety-six predialysis patients (mean age 52 +/- 1 years) with advanced CRF (glomerular filtration rate 7 +/- 1 mL min-1). MAIN OUTCOME MEASURES: Plasma levels of TNF-alpha, subjective global assessment of nutritional status and data on ongoing antihypertensive treatment (ACE-inhibitors, beta blockers, calcium channel blockers and angiotensin II (AII) receptor blockers). RESULTS: Patients treated with ACE-inhibitors (n = 44) had significantly lower plasma TNF-alpha levels (18.5 +/- 1.2 vs. 26.6 +/- 2.2 pg mL-1; P < 0.01) and were less frequently malnourished, relative to 52 patients not treated with ACE-inhibitors. No significant difference in TNF-alpha levels were observed when comparing patients with or without treatment with beta, calcium channel, or AII receptor blockers, respectively. CONCLUSIONS: The present data suggest that the use of ACE-inhibitors is associated with lower plasma TNF-alpha and CRP levels as well as a lower prevalence of malnutrition in patients with advanced CRF. Further studies are needed to establish if there is a casual relationship between these findings and, if so, the molecular mechanism(s).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Interaction of angiotensin II and the insulin-like growth factor system in vascular smooth muscle cells.

We studied the effects and interactions of ANG II and the insulin-like growth factor (IGF) system in cultured rat aortic smooth muscle cells. ANG II (1 microM) and IGF-I (10 nM) stimulated both DNA and protein synthesis. The effects of the two peptides in combination were additive or more than additive. The AT(1) receptor antagonist losartan (10 and 100 microM) blocked their synergistic effect on DNA synthesis. IGF binding protein (IGFBP)-1 inhibited the effect of IGF-I but not that of ANG II on DNA synthesis. IGF-I stimulated gene expression of IGFBP-2 and IGFBP-4. ANG II decreased IGF-I, IGFBP-2, and IGFBP-4 transcripts but increased the IGF-I receptor transcript. IGF-I and ANG II in combination had similar effects on gene expression as ANG II alone. The IGFBP-2 and IGFBP-4 peptides could be detected in the conditioned medium. Our results show that ANG II and IGF-I have synergistic effects on vascular smooth muscle cells and that they interact in several ways.

Angiotensin II↗