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Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 127 records · Page 7Linked to original sources

Fluoride augments the mitogenic and antigenic response of human blood lymphocytes in vitro.

It has been shown that fluoride, the agent responsible for reduction of dental caries worldwide and a recognized proliferative agent, is an adjuvant when given intragastrically to rats. Furthermore, plasma fluoride levels increase in humans after various fluoride treatments. The studies presented here show that fluoride also has the ability to affect the cells of the human immune system. This was tested by measuring the effect of sodium fluoride (NaF) on cytokine production by human whole blood cells stimulated in vitro. These studies revealed that NaF augments the human lymphocyte response from human blood to a mitogen (phytohemagglutinin, PHA) or a specific antigen (morbilli antigen from infected cells, MorbAg). The cytokine interferon-gamma (IFN-gamma), released from activated T and/or NK cells, was significantly (p<0.01) increased when whole blood cells were simultaneously incubated with 0.62 mmol/l NaF and PHA compared to PHA alone. This tendency was also true for NaF and MorbAg. The lymphocyte activation marker interleukin-2 receptor (measured in soluble form) increased after simultaneous stimulation of the cells with PHA and 0.62 mmol/l NaF compared to stimulation with PHA only. However, 0.62 mmol/l NaF did not enhance interleukin-6 release, in blood mainly produced by monocytes. The ability to influence the IFN-gamma release during an immune response could be one of the primary means by which the fluoride ion influences the immune system.

Adjuvants, Immunologic↗

Rat model of Achilles tendon disorder. A pilot study.

Three-month-old male rats were subjected 3 times weekly for 1 h to eccentric exercise of one triceps surae muscle (30 stimulations/min) under general anesthesia in order to induce Achilles tendon disorder corresponding to paratenonitis and tendinosis in man. Net muscle work during the sessions ranged between 0.67 and 4.37 mJ (mean 1.72, SD 0.77). After 9 and 13 sessions, respectively, 2 rats started to show gait alterations during the functional test which was performed 2-3 times weekly. These rats were killed after additional sessions which showed a worsening of the limp. The other trained rats and controls did not limp and were killed after 7-11 weeks. Histologic evaluation of the Achilles tendons from the exercised limb showed in the majority of the cases hypervascularization, increased number of nerve filaments and increased immunoreactivity for substance P and calcitonin gene-related peptide. The tendons from the nonstimulated limb looked normal. The distribution of collagen types I and II appeared normal in the tendon and its insertion to the calcaneus. Inflammation of the epi- and paratenon could be provoked in the rat, but tendon changes corresponding to chronic tendinosis did not develop within 11 weeks with the used training regime. The clinical relevance of this model for chronic tendon disease needs to be evaluated further.

Achilles Tendon↗

Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.

Adult↗

Intensive dose ifosfamide and etoposide with G-CSF for stem cell mobilization in patients with non-Hodgkin's lymphoma.

We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.

Adult↗

Conditions affecting experiences of the quality of psychological debriefings: preliminary findings from a grounded theory study.

The aim of the study was to develop a theoretical understanding of conditions and mechanisms affecting experiences of the quality of emotional debriefings, using a grounded theory approach. Twenty interviews were conducted with experienced male debriefing leaders and participants in the Stockholm fire brigade and the Swedish armored United Nations battalions serving in Bosnia. Data were analyzed according to the constant comparative method. A model was formulated according to which the quality of debriefings is formed by the dynamic interplay between group and debriefing leader characteristics. The key group and debriefing leader quality is security. Furthermore, individual group member resourcefulness and vulnerability, together with the degree of knowledge and support from the management of the organization, also affect experiences of the quality of debriefings. The model is discussed in relation to existing thoughts on potentially favorable mechanisms.

Adult↗

2D-isolation of pure plasma and thylakoid membranes from the cyanobacterium Synechocystis sp. PCC 6803.

Aqueous polymer two-phase partitioning in combination with sucrose density centrifugation offered, for the first time, a 2D-separation method for the isolation of pure plasma and thylakoid membranes from the cyanobacterium Synechocystis 6803 without any cross-contaminations. The purity of the membrane fractions was verified by immunoblot analysis using antibodies against membrane-specific marker proteins. As an initiation of a proteomics project, two prominent proteins, which were observed only in the plasma membrane (Slr1513, a hypothetical protein, and HofG, a general secretion pathway protein), or in the thylakoid membrane (PsaE, a photosystem I protein, and NdhH, a subunit of NADH dehydrogenase), were identified.

Bacterial Proteins↗

The thylakoid lumen of chloroplasts. Isolation and characterization.

The chloroplast compartment enclosed by the thylakoid membrane, the "lumen," is poorly characterized. The major aims of this work were to design a procedure for the isolation of the thylakoid lumen which could be generally used to characterize lumenal proteins. The preparation was a stepwise procedure in which thylakoid membranes were isolated from intact chloroplasts. Loosely associated thylakoid surface proteins were removed, and following Yeda press fragmentation the lumenal content was recovered in the supernatant following centrifugation. The purity and yield of lumenal proteins were determined using appropriate marker proteins specific for the different chloroplast compartments. Quantitative immunoblot analyses showed that the recovery of soluble lumenal proteins was 60-65% (as judged by the presence of plastocyanin), whereas contamination with stromal enzymes was less than 1% (ribulose-bisphosphate carboxylase) and negligible for thylakoid integral membrane proteins (D1 protein). Approximately 25 polypeptides were recovered in the lumenal fraction, of which several were identified for the first time. Enzymatic measurements and/or amino-terminal sequencing revealed the presence of proteolytic activities, violaxanthin de-epoxidase, polyphenol oxidase, peroxidase, as well as a novel prolyl cis/trans-isomerase.

Amino Acid Sequence↗

A novel multi-functional chloroplast protein: identification of a 40 kDa immunophilin-like protein located in the thylakoid lumen.

We describe the identification of the first immunophilin associated with the photosynthetic membrane of chloroplasts. This complex 40 kDa immunophilin, designated TLP40 (thylakoid lumen PPIase), located in the lumen of the thylakoids, was found to play a dual role in photosynthesis involving both biogenesis and intraorganelle signalling. It originates in a single-copy nuclear gene, is made as a precursor of 49.2 kDa with a bipartite lumenal targeting transit peptide, and is characterized by a structure including a cyclophilin-like C-terminal segment of 20 kDa, a predicted N-terminal leucine zipper and a potential phosphatase-binding domain. It can exist in different oligomeric conformations and attach to the inner membrane surface. It is confined predominantly to the non-appressed thylakoid regions, the site of protein integration into the photosynthetic membrane. The isolated protein possesses peptidyl-prolyl cis-trans isomerase protein folding activity characteristic of immunophilins, but is not inhibited by cyclosporin A. TLP40 also exerts an effect on dephosphorylation of several key proteins of photosystem II, probably as a constituent of a transmembrane signal transduction chain. This first evidence for a direct role of immunophilins in a photoautotrophic process suggests that light-mediated protein phosphorylation in photosynthetic membranes and the role of the thylakoid lumen are substantially more complex than anticipated.

Amino Acid Sequence↗

Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by gamma-hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B) receptors.

Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are associated with a decrease in firing rate, a regularisation of firing pattern and a decrease in burst activity of midbrain dopamine (DA) neurons in the substantia nigra (SN). In the present study we compared the ability of the novel GABA(B) receptor antagonist SCH 50911 and the selective antagonist of GHBA binding sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg, i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32 mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not affect the baclofen-induced changes in neuronal activity. Neither was the drug able to influence the GHBA-induced alterations in firing rate or in burst activity, although NCS-382 to some extent antagonised the regularisation of the firing pattern observed following low doses of GHBA (< or =100 mg/kg). The results of the present study give further support for the notion that the GHBA-induced changes in neuronal activity of nigral dopamine neurons are mediated by stimulation of GABA(B) receptors.

Animals↗

The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17.

Full exon-intron structures are presented for the NIK serine/threonine protein kinase gene and a novel gene termed C17orf1. By in situ hybridisation and radiation hybrid mapping, a cosmid (cDD-Z) that contains regions of both of these genes has been localised between markers D17S800 and D17S791 at chromosome 17q21. The two genes are thus positional candidates for the mutant locus underlying frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), a disease for which NIK is also a good biological candidate. Using exon-intron maps, a genomic DNA sequencing based mutation screen has been performed for the NIK and C17orf1 genes in a chromosome 17-linked FTDP-17 pedigree. Two silent single-base variations were detected in C17orf1. No alterations were restricted to DNA samples from patients, thus excluding the C17orf1 and NIK genes as likely sites of mutation FTDP-17.

Carrier Proteins↗

Determination of aflatoxicol in human urine by immunoaffinity column clean-up and liquid chromatography.

A method for the determination of aflatoxicol in urine has been developed. The urine samples were cleaned up by an automated procedure using immunoaffinity columns before analysis by high-performance liquid chromatography and fluorescence detection. Post-column derivatization with bromine allowed the simultaneous determination of aflatoxicol and aflatoxins B1, B2, G1, G2, M1, and Q1. Average recovery of aflatoxicol was 99% in the range 4-40 pg ml-1 of spiked urine samples. The relative standard deviations were all between 1% and 3%. The limit of detection was 1 pg ml-1 urine. Authentic samples from exposed feed-factory workers were analysed, but aflatoxin levels were found to be below the detection limit.

Aflatoxins↗

Mild experimental exacerbation of asthma induced by individualised low-dose repeated allergen exposure. A double-blind evaluation.

Low doses of environmental allergens have been proposed to increase bronchial hyperreactivity in sensitised individuals, without causing immediate asthmatic reactions. The primary aim of the present study was to evaluate whether repeated low doses of allergen, that do not cause overt bronchoconstriction, cause augmented non-specific bronchial reactivity. A secondary aim was to evaluate whether any changes in reactivity are associated with increased variability of lung function, and whether signs of inflammatory activity could be found. To do this, mild asthmatic patients without regular symptoms, but with both immediate and late reactions in response to a high dose of inhaled cat allergen extract, were included in a double blind, placebo controlled, cross-over study in which a low dose of allergen was administered on four consecutive days (Monday to Thursday). The dose of allergen was individualised for each patient, and was calculated to be 25% of the total dose given to produce an immediate and late response at screening. Repeated low dose allergen exposure produced a significant increase in methacholine reactivity compared to placebo, whereas FEV1 in the morning did not significantly change during the allergen week. Each low dose allergen exposure caused small changes in FEV1 (approximately 7% drop), which was significant vs. placebo only on day 2 (Tuesday). During the allergen week, six of eight patients reported asthma symptoms on at least one occasion, and variability in lung function, measured with a portable spirometer, was increased. Repeated low doses of allergen also produced a significant increase of P-ECP vs. placebo, without a significant rise in circulating eosinophils. However, no significant changes in circulating CD3, CD4, CD8, CD19, or CD25 cells were found, evaluated by FACS analysis. We conclude that low doses of allergen produce signs of a mild exacerbation of asthma, including increased bronchial reactivity to methacholine. This clinical model may be useful to evaluate both the pathophysiological mechanisms of asthma, and the effects of novel anti-asthma drugs.

Adult↗

Protein phosphorylation and redox sensing in chloroplast thylakoids.

Transduction of light dependent signals to redox sensitive kinases in photosynthetic membranes modulates energy transfer to the photochemical reaction centres and regulates biogenesis, stability and turnover of thylakoid protein complexes. The occupancy of the quinol-oxidation site of the cytochrome bf complex by plastoquinol and the redox state of protein thiol groups act as elements of the signal transducing chains.

Chloroplasts↗

Urinary albumin excretion and heart rate variability in obese women.

OBJECTIVE: The aim of this work was to examine the relationship between cardiac autonomic function and urinary albumin excretion in obesity. SUBJECTS: These were 27 obese non-diabetic postmenopausal women and 18 non-obese healthy postmenopausal women. MEASUREMENTS: Urinary albumin excretion as well as plasma nitrate, both indices of capillary function, were measured. Power spectral analysis of heart rate variability was performed, as a measurement of vagal function. An oral glucose tolerance test (OGTT) was performed and blood lipids were analysed. RESULTS: The obese women were characterized by higher fasting insulin, sum of glucose, triglycerides and lower high density lipoprotein cholesterol (HDL), the latter of borderline significance, than controls. Urinary albumin excretion (UAE), plasma nitrate and heart rate variability were not different between obese and control women. However, in obese women log UAE correlated positively with systolic and diastolic blood pressure, and inversely with heart rate variability, the latter independent of body mass index (BMI) and the waist/hip circumference ratio. CONCLUSION: It was concluded that this inverse association between UAE and parasympathetic activity in obese women may be an early sign of derangements of endothelial function and autonomic nervous system control, which may contribute to the increased risk of cardiovascular mortality in abdominal obesity.

Aged↗

Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderate-to-severe, chronic heart failure.

AIMS: To evaluate the feasibility of a nurse-monitored, outpatient-care program for elderly patients previously hospitalized with chronic heart failure. METHODS AND RESULTS: Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a randomized study to compare the effect of a nurse-monitored, outpatient-care programme aiming at symptom management, with conventional care. The inclusion criteria were patients classified in New York Heart Association classes III-IV, age 65 years, and eligibility for an outpatient follow-up programme. The total in-hospital population of patients discharged with a heart-failure diagnosis was surveyed. Eighty-nine per cent of all the hospitalized patients (n=1541) were 65 years old. Of these, 69% (n=1058) were treated in the medical wards which were screened. The study criteria were met by 158 patients (15%). No visits to the nurse occurred in 23 cases among the 79 patients randomized to the structured-care group (29%), mainly on account of death or fatigue. The numbers of hospitalizations and hospital days did not differ between the structured-care and the usual-care groups. CONCLUSIONS: Given the selection criteria and the outline of the interventions, the outpatient, nurse-monitored, symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe, chronic heart failure, mainly because of the small proportion of eligible patients and the high drop-out rate. Management of these patients would have to be more adjusted to their home situation.

Aged↗