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Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Dephosphorylation of photosystem II reaction center proteins in plant photosynthetic membranes as an immediate response to abrupt elevation of temperature.

Kinetic studies of protein dephosphorylation in photosynthetic thylakoid membranes revealed specifically accelerated dephosphorylation of photosystem II (PSII) core proteins at elevated temperatures. Raising the temperature from 22 degrees C to 42 degrees C resulted in a more than 10-fold increase in the dephosphorylation rates of the PSII reaction center proteins D1 and D2 and of the chlorophyll a binding protein CP43 in isolated spinach (Spinacia oleracea) thylakoids. In contrast the dephosphorylation rates of the light harvesting protein complex and the 9-kD protein of the PSII (PsbH) were accelerated only 2- to 3-fold. The use of a phospho-threonine antibody to measure in vivo phosphorylation levels in spinach leaves revealed a more than 20-fold acceleration in D1, D2, and CP43 dephosphorylation induced by abrupt elevation of temperature, but no increase in light harvesting protein complex dephosphorylation. This rapid dephosphorylation is catalyzed by a PSII-specific, intrinsic membrane protein phosphatase. Phosphatase assays, using intact thylakoids, solubilized membranes, and the isolated enzyme, revealed that the temperature-induced lateral migration of PSII to the stroma-exposed thylakoids only partially contributed to the rapid increase in the dephosphorylation rate. Significant activation of the phosphatase coincided with the temperature-induced release of TLP40 from the membrane into thylakoid lumen. TLP40 is a peptidyl-prolyl cis-trans isomerase, which acts as a regulatory subunit of the membrane phosphatase. Thus dissociation of TLP40 caused by an abrupt elevation in temperature and activation of the membrane protein phosphatase are suggested to trigger accelerated repair of photodamaged PSII and to operate as possible early signals initiating other heat shock responses in chloroplasts.

Chlorophyll↗
PubMed2000

The thylakoid FtsH protease plays a role in the light-induced turnover of the photosystem II D1 protein.

The photosystem II reaction center D1 protein is known to turn over frequently. This protein is prone to irreversible damage caused by reactive oxygen species that are formed in the light; the damaged, nonfunctional D1 protein is degraded and replaced by a new copy. However, the proteases responsible for D1 protein degradation remain unknown. In this study, we investigate the possible role of the FtsH protease, an ATP-dependent zinc metalloprotease, during this process. The primary light-induced cleavage product of the D1 protein, a 23-kD fragment, was found to be degraded in isolated thylakoids in the dark during a process dependent on ATP hydrolysis and divalent metal ions, suggesting the involvement of FtsH. Purified FtsH degraded the 23-kD D1 fragment present in isolated photosystem II core complexes, as well as that in thylakoid membranes depleted of endogenous FtsH. In this study, we definitively identify the chloroplast protease acting on the D1 protein during its light-induced turnover. Unlike previously identified membrane-bound substrates for FtsH in bacteria and mitochondria, the 23-kD D1 fragment represents a novel class of FtsH substrate-functionally assembled proteins that have undergone irreversible photooxidative damage and cleavage.

ATP-Dependent Proteases↗
PubMed2000

Gram-positive bacteria are potent inducers of monocytic interleukin-12 (IL-12) while gram-negative bacteria preferentially stimulate IL-10 production.

Interleukin-10 (IL-10) and IL-12 are two cytokines secreted by monocytes/macrophages in response to bacterial products which have largely opposite effects on the immune system. IL-12 activates cytotoxicity and gamma interferon (IFN-gamma) secretion by T cells and NK cells, whereas IL-10 inhibits these functions. In the present study, the capacities of gram-positive and gram-negative bacteria to induce IL-10 and IL-12 were compared. Monocytes from blood donors were stimulated with UV-killed bacteria from each of seven gram-positive and seven gram-negative bacterial species representing both aerobic and anaerobic commensals and pathogens. Gram-positive bacteria induced much more IL-12 than did gram-negative bacteria (median, 3,500 versus 120 pg/ml at an optimal dose of 25 bacteria/cell; P < 0.001), whereas gram-negative bacteria preferentially stimulated secretion of IL-10 (650 versus 200 pg/ml; P < 0.001). Gram-positive species also induced stronger major histocompatibility complex class II-restricted IFN-gamma production in unfractionated blood mononuclear cells than did gram-negative species (12,000 versus 3,600 pg/ml; P < 0.001). The poor IL-12-inducing capacity of gram-negative bacteria was not remediated by addition of blocking anti-IL-10 antibodies to the cultures. No isolated bacterial component could be identified that mimicked the potent induction of IL-12 by whole gram-positive bacteria, whereas purified LPS induced IL-10. The results suggest that gram-positive bacteria induce a cytokine pattern that promotes Th1 effector functions.

Aerobiosis↗
PubMed2000

Early changes in longitudinal performance predict future improvement in global left ventricular function during long term beta adrenergic blockade.

OBJECTIVE: Contraction of longitudinal and subendocardial myocardial muscle fibres is reflected in descent of the atrioventricular (AV) plane. The aim was therefore to determine whether beta blocker treatment with prolongation of diastole might result in improved function as reflected by AV plane movements in patients with chronic heart failure. DESIGN: Double blind, randomised, placebo controlled and open intervention study. SETTING: University hospital. PATIENTS: Patients with congestive heart failure: placebo controlled (n = 26) and an open protocol (n = 15). INTERVENTIONS: 12 months of metoprolol treatment. MAIN OUTCOME MEASURES: Short axis and long axis echocardiography, invasive haemodynamics, radionuclide angiography. RESULTS: Recovery of systolic and diastolic function during metoprolol treatment was reflected by early changes in mean (SD) AV plane amplitude, from 5.3 (2.0)% to 7.1 (3.2)% and 7.8 (3. 1)% (at 3 and 12 months, respectively; p < 0.05). In a multivariate analysis, only the change in AV plane amplitude by three months was independently associated with improvement in pulmonary capillary wedge pressure by six months (r = 0.80, p = 0.017). Change in AV plane amplitude by three months was also a better predictor of improvement in ejection fraction by 12 months (r = 0.78, p < 0.001) than changes in radionuclide ejection fraction by three months (r = 0.34, p = 0.049). CONCLUSIONS: Improvement in longitudinal contraction was closely associated with a decrease in left ventricular filling pressure during metoprolol treatment. This association was stronger than changes in short axis performance or radionuclide ejection fraction, emphasising the importance of AV plane motion for left ventricular filling and systolic performance in patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2000

Hormone replacement therapy in postmenopausal women with diabetes mellitus: a risk-benefit assessment.

Hormone replacement therapy (HRT) has been shown to be beneficial in reducing osteoporosis and alleviating climacteric symptoms. HRT has been suggested to reduce the risk for coronary heart disease (CHD), but data are controversial. Unopposed estradiol therapy seems to have a favourable effect on lipid profile and glucose tolerance whereas addition of a progestogen may attenuate these favourable metabolic changes. Data on HRT in women with diabetes mellitus are scarce but of potential interest since these women are often characterised by hyperandrogenicity, insulin resistance and dyslipidaemia and are at a high risk for developing CHD. Present evidence suggests that short term unopposed oral estradiol therapy has a beneficial effect on glucose homeostasis, lipid profile and fibrinolytic activity, which may be compatible with a reduced risk for CHD. Accordingly, it may be hypothesised that HRT in women with diabetes mellitus may be at least as beneficial as in women without diabetes mellitus. However, women with diabetes mellitus are at increased underlying risk for venous thromboembolism and endometrial cancer. Whether HRT further increases this risk is not yet clear, but this possibility must be considered. It is, however, likely that the benefits with HRT in postmenopausal women with diabetes mellitus outweigh the risks, but randomised studies are required before any more definite risk-benefit assessment can be made long term.

Diabetes Complications↗
PubMed2000

Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy.

Growing evidence suggests that autoimmune mechanisms play an important role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The aim of the study was to evaluate the effects of transfer of lymphocytes from patients with DCM into severe combined immunodeficiency (SCID) mice on the heart structure and function. Thirty CB-17 SCID (6-8 weeks old) mice were used and divided into 3 groups (n = 10). Mice were injected intraperitoneally with up to 25 x 10(6) peripheral blood lymphocytes (PBL) from either patients with DCM which contain human autoantibodies against cardiac beta1-adrenergic receptors and M2-muscarinic receptors (DCM group) or PBL from healthy controls (control-H group). Ten mice did not receive any injections and were used as baseline controls (control-N group). Echocardiography and morphological studies were performed seventy five days after the transfer. Results showed that in DCM group, left ventricle dimensions (LVD) in diastole were increased (4.2 +/- 0.1mm) as compared to both control-H group (3.8 +/- 0.1mm) and control-N group (3.6 +/- 0.1 mm) (p < 0.01). Further, there was a trend for increased LVD in systole. Fractional shortening was not different between groups. Histological evaluation revealed accumulation of human lymphocytes in the capillaries and scarce infiltration of the lymphocytes in the hearts from DCM group. Diffuse fibrosis was significant increased in DCM mice as compared to mice receiving PBL from normal subjects (2.2 +/- 0.3% vs. 0.8 +/- 0.1%, p < 0.01). In conclusion, transfer of the PBL from the patients with DCM was able to induce early stage of heart dilatation in SCID mice. These data provide for the first time the direct evidence supporting that the autoimmune mechanism is important in the pathogenesis of human DCM.

Animals↗
PubMed1999

A cyclophilin-regulated PP2A-like protein phosphatase in thylakoid membranes of plant chloroplasts.

Dephosphorylation of central photosynthetic proteins regulates their turnover in plant thylakoid membranes. A membrane protein phosphatase from spinach thylakoids was purified 13000-fold using detergent-engaged FPLC. The purified enzyme exhibited characteristics typical of eukaryotic Ser/Thr phosphatases of the PP2A family in that it was inhibited by okadaic acid (IC(50) = 0.4 nM) and tautomycin (IC(50) = 25 nM), irreversibly bound to microcystin-agarose, and recognized by a polyclonal antibody raised against a recombinant catalytic subunit of human PP2A. Furthermore, the anti-PP2A antibody inhibited protein dephosphorylation in isolated thylakoids. The phosphatase copurified with TLP40, a cyclophilin-like peptidyl-prolyl isomerase located in the thylakoid lumen. TLP40 could be released from the phosphatase immobilized on microcystin-agarose by high-salt treatment. Binding of cyclosporin A (CsA) to TLP40 led to thylakoid phosphatase activation, while cyclophilin substrates, prolyl-containing oligopeptides, inhibited protein dephosphorylation. This dephosphorylation could be modulated by CsA or oligopeptides only after the thylakoids had been ruptured to expose the lumenal membrane surface where the TLP40 is located. Regulation of the PP2A-like phosphatase at the outer thylakoid surface is likely to operate via reversible binding of TLP40 to the inner membrane surface. This is a first example of transmembrane regulation in which the activity of phosphatase is altered by the binding of a cyclophilin to a site other than the active one. We propose that signaling from TLP40 to the protein phosphatase coordinates dephosphorylation and protein folding, two processes required for protein turnover during the repair of photoinhibited photosystem II reaction centers.

Amino Acid Sequence↗
PubMed1999

Protein prenylation in spinach chloroplasts.

Protein prenylation in plants was studied by in vivo metabolic (3)H-mevalonate labeling in combination with a range of protein synthesis inhibitors. In spinach cotyledons, this posttranslational protein modification was found to be divided into two categories, one representing the conventional prenylation involving farnesyl and geranylgeranyl groups bound to cysteine residues via thioether linkages. This category revealed a similar pattern of prenylated proteins to that observed in mammalian cells and depends on nuclear gene expression. The other category was shown to represent a type of prenylation confined to chloroplasts. It depends on plastid gene expression and does not involve a thioether bond. The modifying isoprenoid could be released from the chloroplastic polypeptides by alkaline treatment and was identified as phytol upon GC-MS analysis. The phytol could readily be derived from all-trans-[(3)H]farnesol, which, like all-trans-[(3)H]geranylgeraniol, was taken up by the cotyledons, resulting in incorporation of radiolabel into proteins.

Animals↗
PubMed1999

Regulation of thylakoid protein phosphorylation at the substrate level: reversible light-induced conformational changes expose the phosphorylation site of the light-harvesting complex II.

Light-dependent activation of thylakoid protein phosphorylation regulates the energy distribution between photosystems I and II of oxygen-evolving photosynthetic eukaryotes as well as the turnover of photosystem II proteins. So far the only known effect of light on the phosphorylation process is the redox-dependent regulation of the membrane-bound protein kinase(s) activity via plastoquinol bound to the cytochrome bf complex and the redox state of thylakoid dithiols. By using a partially purified thylakoid protein kinase and isolated native chlorophyll (chl) a/b light-harvesting complex II (LHCII), as well as recombinant LHCII, we find that illumination of the chl-protein substrate exposes the phosphorylation site to the kinase. Light does not activate the phosphorylation of the LHCII apoprotein nor the recombinant pigment-reconstituted complex lacking the N-terminal domain that contains the phosphothreonine site. The suggested light-induced conformational change exposing the N-terminal domain of LHCII to the kinase is evidenced also by an increase in its accessibility to tryptic cleavage after light exposure. Light activates preferentially the trimeric form of LHCII, and the process is paralleled by chl fluorescence quenching. Both phenomena are slowly reversible in darkness. Light-induced exposure of the LHCII N-terminal domain to the endogenous protein kinase(s) and tryptic cleavage occurs also in thylakoid membranes. These results demonstrate that light may regulate thylakoid protein phosphorylation not only via the signal transduction chain connecting redox reactions to the protein kinase activation, but also by affecting the conformation of the chl-protein substrate.

Journal Article↗
PubMed1999

ASHAP: a regimen for cytoreduction of refractory or recurrent Hodgkin's disease.

Patients with Hodgkin's disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin's disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin's disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of </=6 months, predicted a poor response to ASHAP. A short program of treatment with ASHAP is an effective tumor debulking approach in patients previously treated with both or either ABVD and MOPP, before ABMT.

Adolescent↗
PubMed1999

GTP bound to chloroplast thylakoid membranes is required for light-induced, multienzyme degradation of the photosystem II D1 protein.

Even though light is the driving force in photosynthesis, it also can be harmful to plants. The water-splitting photosystem II is the main target for this light stress, leading to inactivation of photosynthetic electron transport and photooxidative damage to its reaction center. The plant survives through an intricate repair mechanism involving proteolytic degradation and replacement of the photodamaged reaction center D1 protein. Based on experiments with isolated chloroplast thylakoid membranes and photosystem II core complexes, we report several aspects concerning the rapid turnover of the D1 protein. (i) The primary cleavage step is a GTP-dependent process, leading to accumulation of a 23-kDa N-terminal fragment. (ii) Proteolysis of the D1 protein is inhibited below basal levels by nonhydrolyzable GTP analogues and apyrase treatment, indicating the existence of endogenous GTP tightly bound to the thylakoid membrane. This possibility was corroborated by binding studies. (iii) The proteolysis of the 23-kDa primary degradation fragment (but not of the D1 protein) is an ATP- and zinc-dependent process. (iv) D1 protein degradation is a multienzyme event involving a strategic (primary) protease and a cleaning-up (secondary) protease. (v) The chloroplast FtsH protease is likely to be involved in the secondary degradation steps. Apart from its significance for understanding the repair of photoinhibition, the discovery of tightly bound GTP should have general implications for other regulatory reactions and signal transduction pathways associated with the photosynthetic membrane.

Journal Article↗
PubMed1999

Thylakoid protein phosphorylation and the thiol redox state.

Illumination of thylakoid membranes leads to the phosphorylation of a number of photosystem II-related proteins, including the reaction center proteins D1 and D2 as well as the light-harvesting complex (LHCII). Regulation of light-activated thylakoid protein phosphorylation has mainly been ascribed to the redox state of the electron carrier plastoquinone. In this work, we show that this phosphorylation in vitro is also strongly influenced by the thiol disulfide redox state. Phosphorylation of the light-harvesting complex of photosystem II was found to be favored by thiol-oxidizing conditions and strongly downregulated at moderately thiol-reducing conditions. In contrast, phosphorylation of the photosystem II reaction center proteins D1 and D2 as well as that of other photosystem II subunits was found to be stimulated up to 2-fold by moderately thiol-reducing conditions and kept at a high level also at highly reducing conditions. These responses of the level of thylakoid protein phosphorylation to changes in the thiol disulfide redox state are reminiscent of those observed in vivo in response to changes in the light intensity and point to the possibility of a second loop of redox regulation of thylakoid protein phosphorylation via the ferredoxin-thioredoxin system.

Adenosine Triphosphatases↗
PubMed1999

Isolation of a highly active PSII-LHCII supercomplex from thylakoid membranes by a direct method.

We have developed a simple and novel method to isolate a highly pure and active photosystem (PS) II complex, directly from thylakoid membranes. This complex is a discrete particle and contains all the proteins of the oxygen evolving complex and a set of chlorophyll alb binding proteins. The intactness of both the donor side and the acceptor side has resulted in a very high oxygen evolution activity and therefore offers a superior experimental system to that of PSII enriched membrane fragments in which there is heterogeneity in activities and biochemical composition.

Cell Membrane↗
PubMed1999

Potential risk of beta-blockade withdrawal in congestive heart failure due to abrupt autonomic changes.

Beta-Blockers reduce mortality in patients with congestive heart failure and a proposed mechanism has been changes of autonomic tone. Heart rate variability is a non-invasive tool to estimate cardiac autonomic tone. The aim was to study changes of heart rate variability in patients with congestive heart failure on placebo, on the beta1-selective antagonist metoprolol or 24 h after metoprolol withdrawal. Forty-five patients with congestive heart failure were studied with Holter recordings. Heart rate variability measurements were performed before, after 6-12 months of treatment with 150 mg metoprolol/placebo, or 24 h after discontinued metoprolol. After treatment, patients on beta-blockade had a significantly longer mean RR interval and changes of heart rate variability, suggesting elevated vagal tone. Patients monitored in the rebound phase of beta-blocker withdrawal had a significant vagal reduction to the level of the placebo group. There was also a nonsignificant trend towards increased sympathetic tone (LF/HF over 24 h), compared with the beta-blockade group. Heart rate variability indicates an elevated vagal tone during treatment with metoprolol but beta-blockade withdrawal shifts the autonomic balance towards lower vagal and higher sympathetic tone within 24 h. These results could imply a potential risk when abruptly discontinuing beta-blockade medication in these patients.

Adolescent↗
PubMed1999

[Sensitive quality indicators stimulate improvement of care].

For the past four years, 52 of the approximately 80 departments of medicine in Sweden have collected data on key indicators of quality of care with regards to acute myocardial infarction, stroke, anticoagulant treatment, and diabetes. The results are analysed centrally, each department being supplied with feedback in the form of overall results, and comparison of its own values with the respective means. Gradual general improvement has been discernible over time, though there is still room for improvement at some departments. There have been isolated instances of manifest changes in indicator values associated with major departmental reorganisation, probably reflecting real deterioration in quality of care. Thus, indicator monitoring would appear a sensitive means of promoting qualitative improvement.

Anticoagulants↗
PubMed1999

A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space.

In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+, helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+/CD3+8+ in BAL than in blood (3.4 vs 1.7; P = 0.001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment. We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.

Antigens, CD↗