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Biomedical subjects

L Bengtsson

Publications and source records attributed to L Bengtsson.

At least 19 recordsLinked to original sources
PubMed2001

Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane.

The nuclear envelope (NE) is one of the least characterized structures of eukaryotic cells. The study of its functional roles is hampered by the small number of proteins known to be specifically located to it. Here, we present a comprehensive characterization of the NE proteome. We applied different fractionation procedures and isolated protein subsets derived from distinct NE compartments. We identified 148 different proteins by 16-benzyl dimethyl hexadecyl ammonium chloride (16-BAC) gel electrophoresis and matrix-assisted laser desorption ionization (MALDI) mass spectrometry; among them were 19 previously unknown or noncharacterized. The identification of known proteins in particular NE fractions enabled us to assign novel proteins to NE substructures. Thus, our subcellular proteomics approach retains the screening character of classical proteomic studies, but also allows a number of predictions about subcellular localization and interactions of previously noncharacterized proteins. We demonstrate this result by showing that two novel transmembrane proteins, a 100-kDa protein with similarity to Caenorhabditis elegans Unc-84A and an unrelated 45-kDa protein we named LUMA, reside in the inner nuclear membrane and likely interact with the nuclear lamina. The utility of our approach is not restricted to the investigation of the NE. Our approach should be applicable to the analysis of other complex membrane structures of the cell as well.

Animals↗
PubMed2001

Elevations in antidiuretic hormone and aldosterone as possible causes of fluid retention in the Maze procedure.

BACKGROUND: Reduced levels of atrial natriuretic peptide (ANP) has been suggested as a cause of fluid retention after combined Maze and valvular surgery. This study aimed to assess hormonal activation in the perioperative setting of isolated Maze procedures. METHODS: Changes in ANP, brain natriuretic peptide (BNP), antidiuretic hormone (ADH), aldosterone, and angiotensin II were measured in 16 patients (mean age 53+/-9 years) without concomitant heart disease undergoing the Maze (III) procedure. Ten matched patients (mean age 56+/-9 years) undergoing multivessel coronary artery bypass grafting served as controls. Measurements with hemodynamic correlates were obtained at baseline and after ventricular pacing (100 stimulations/minute), directly preoperatively, postoperatively and the first postoperative day. Weight gain and diuretic requirements were recorded. RESULTS: The major differences in hormonal response were significantly higher plasma levels of ADH (Maze preoperative 1.1+/-0.4, postoperative 24.9+/-16.7 pmol/L; controls preoperative 1.1+/-0.1, postoperative 3.7+/-3.5 pmol/L) and aldosterone (Maze preoperative 106+/-94, postoperative 678+/-343 pmol/L; controls preoperative 124+/-79, postoperative 171+/-93 pmol/L) in the Maze group on the first postoperative day (p < 0.001). Preoperative baseline plasma levels of ANP and pulmonary capillary wedge pressures (PCWP) were higher in the Maze group but this difference was abolished by pacing, and postoperatively, ANP levels changed in parallel to the PCWP in both groups. Diuretic requirements were significantly higher in the Maze group. CONCLUSIONS: Substantial increases in ADH and aldosterone were observed after the Maze procedure, indicating these hormones as important determinants in postoperative fluid retention. The role for ANP in this setting may be a less prominent than previously reported.

Adult↗
PubMed2001

Fast track as a routine for open heart surgery.

OBJECTIVE: Evaluation of thoracic epidural analgesia (TEA), normothermic cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine procedure for fast track open heart surgery. METHODS: Consecutive patients (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the combination of general anaesthesia using ultra-short acting opiates, TEA, normothermic CBP, normothermic whole blood cardioplegia. Operative procedures included coronary artery bypass grafting (CABG), valve replacement, combined CABG and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent were in Tuman score 0--5 and 20% in score >5. RESULTS: All patients were extubated within 10 min after skin closure. There was one myocardial infarction. Four percent were shortly treated with cathecholamines. Postoperative atrial fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were encountered. No neurological disturbance related to the use of TEA was seen. Seven patients were reoperated because of bleeding. Blood transfusion was given to 6.4% of the patients. Mortality was 0.8%. CONCLUSIONS: The combined methods provides a way for routine immediate postoperative extubation, with low morbidity and short hospital stay.

Adult↗
PubMed2001

Identification of tyrosine-phosphorylated proteins associated with the nuclear envelope.

The nuclear envelope separates the nucleoplasm from the rest of the cell. Throughout the cell cycle, its structural integrity is controlled by reversible protein phosphorylation. Whereas its phosphorylation-dependent disassembly during mitosis is well characterized, little is known about phosphorylation events at this structure during interphase. The few characterized examples cover protein phosphorylation at serine and threonine residues, but not tyrosine phosphorylation at the nuclear envelope. Here, we demonstrate that tyrosine phosphorylation and dephosphorylation occur at the nuclear envelope of intact Neuro2a mouse neuroblastoma cells. Tyrosine kinase and phosphatase activities remain associated with purified nuclear envelopes. A similar pattern of tyrosine-phosphorylated nuclear envelope proteins suggests that the same tyrosine kinases act at the nuclear envelope of intact cells and at the purified nuclear envelope. We have also identified eight tyrosine-phosphorylated nuclear envelope proteins by 2D BAC/SDS/PAGE, immunoblotting with phosphotyrosine-specific antibodies, tryptic in-gel digestion, and MS analysis of tryptic peptides. These proteins are the lamina proteins lamin A, lamin B1, and lamin B2, the inner nuclear membrane protein LAP2beta, the heat shock protein hsc70, and the DNA/RNA-binding proteins PSF, hypothetical 16-kDa protein, and NonO, which copurify with the nuclear envelope.

Animals↗
PubMed2001

In vitro endothelialization of bioprosthetic heart valves provides a cell monolayer with proliferative capacities and resistance to pulsatile flow.

OBJECTIVES: Degeneration of bioprosthetic heart valves has been suggested to be at least partly an immunogenic reaction toward the xenogeneic tissue. An autologous endothelial lining has been proposed to overcome this problem. We examined in vitro endothelialization of such tissue and retention of endothelial cells after exposure to flow resembling the in vivo situation. METHODS: Cultured human saphenous vein endothelial cells were used to in vitro endothelialize photo-oxidized bioprosthetic heart valves. The endothelialized valves were mounted in a specially designed flow device, creating a pulsatile flow through the valve. Maintenance of a confluent cell layer and deposition of basement membrane markers were determined with immunohistochemical labeling. RESULTS: Labeling of the main components of the basement membrane, laminin and collagen type IV, was verified within 6 hours after in vitro endothelialization. Under static conditions, 4-mm wide denudations were completely re-endothelialized in 4 days, which was similar to the growth rate on gelatin-coated cell culture plastic, which served as a control material. After exposure of endothelialized valves to pulsatile flows for 24 hours (80 beats/min, 3.4 L/min), there were minimal cell losses from the bioprostheses. The cell layer adapted to the pulsatile flow, as verified by rearrangement of morphology and intracellular stress fibers. CONCLUSIONS: This study shows the feasibility of in vitro endothelialization of photo-oxidized bioprosthetic heart valves. The cells are able to withstand a pulsatile flow in vitro, to develop basement membrane-like structures, and to re-endothelialize denuded areas. This technology may be used to enhance the performance of bioprosthetic heart valve prostheses.

Basement Membrane↗
PubMed2000

Interpreting differential temperature trends at the surface and in the lower troposphere

Estimated global-scale temperature trends at Earth's surface (as recorded by thermometers) and in the lower troposphere (as monitored by satellites) diverge by up to 0.14 degrees C per decade over the period 1979 to 1998. Accounting for differences in the spatial coverage of satellite and surface measurements reduces this differential, but still leaves a statistically significant residual of roughly 0.1 degrees C per decade. Natural internal climate variability alone, as simulated in three state-of-the-art coupled atmosphere-ocean models, cannot completely explain this residual trend difference. A model forced by a combination of anthropogenic factors and volcanic aerosols yields surface-troposphere temperature trend differences closest to those observed.

Journal Article↗
PubMed2000

The Maze operation for treatment of atrial fibrillation. Early clinical experience in a Scandinavian institution.

The Maze operation is a potentially curative surgical option in patients with disabling atrial fibrillation (AF) refractory to conventional treatment. The aim of this study was to evaluate the initial 4-year Maze experience in our institution. The study included 26 patients (19 males, mean age 55 years) who had undergone the Maze (III) operation between 1994 and 1998. Nine patients had surgery for concomitant heart disease. Follow-up was 3-55 (median 18) months. No deaths or neurological complications occurred; 22 patients are at present in regular sinus-, or junctional rhythm, 2 patients have permanent atrial pacing for symptomatic sinus node dysfunction, and 2 patients have had persistent AF, post surgery. Sinus node dysfunctions were detected in five patients, though not requiring pacemakers. Out of the total 26 patients, 23 are free of anti-arrhythmic drugs. Echocardiographic signs of left atrial contraction were recorded in 50% of the patients. The Maze operation offers a safe alternative to conventional therapy, with attractive results justifying expansion in the use of this treatment for AF.

Adult↗
PubMed1998

Time-course for in vitro development of basement membrane, gap junctions, and repair by adult endothelial cells seeded on precoated ePTFE.

OBJECTIVES: To establish some functional characteristics after in vitro endothelialisation of precoated ePTFE grafts. MATERIALS AND METHODS: Saphenous vein endothelial cells were confluently seeded on human serum-precoated ePTFE. Collagen I-precoated ePTFE served as control. Time-courses for development of laminin, collagen IV and connexin43 was followed-up with immunofluorescence. Endothelial migration and proliferation was studied with cresyl violet staining and tritiated thymidine-labelling. RESULTS: Six hours post-seeding, basement membrane components were visualised subendothelially as thin fibrils. After 24 h, there was a distinct fibril network, which did not seem to be further enhanced. Connexin43 was detected 6 h post-seeding, and the number of intercellular connections appeared to be similar up to day 7. The time-courses were similar on serum- and collagen I-precoated ePTFE. Endothelialisation of a 4 mm wide gap showed migrating fronts largely composed of proliferating cells. The process was completed within 10 days on collagen I-precoated ePTFE, and 15 days on serum-precoated ePTFE. CONCLUSIONS: These findings suggest human endothelial cells, seeded on precoated ePTFE, maintain some differentiated functions seen in vivo. This is of importance for cell retention, functionality and endothelial repair of in vitro endothelialised ePTFE-grafts after implantation in man.

Basement Membrane↗
PubMed1998

One-week omeprazole treatment in the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: Symptoms of gastro-oesophageal reflux are common, and currently available methods for diagnosing reflux disease are expensive and uncomfortable for the patient. The diagnostic value of a treatment test with omeprazole is unclear. METHODS: Patients with dyspepsia including heartburn admitted for upper gastrointestinal endoscopy were studied in a prospective, randomized, double-blind Scandinavian multicentre study. Before entry 188 patients were enrolled, and 160 were randomized to 1-week treatment with 20 mg omeprazole twice daily or placebo. Gastro-oesophageal reflux disease (GERD) was defined as reflux oesophagitis Savary-Miller grades II-III at endoscopy or pH < 4 exceeding 4% of the total time at 24-h oesophageal pH-monitoring and was found in 135 patients. The treatment test was considered positive when the patient's symptoms improved during the treatment week compared with the pretreatment day. RESULTS: The sensitivity in diagnosing reflux disease was 71-81% with omeprazole as a diagnostic test, compared with 36-47% for placebo during treatment days 3-7. The specificity was similar for the two treatment arms during the first days of the study. During the end of the week a larger proportion of the patients with normal endoscopy and pH test responded to omeprazole treatment, giving omeprazole lower specificity than placebo. The investigators' overall evaluation of whether the patient was a responder to the test had a sensitivity of 75% and a specificity of 55% in the omeprazole-treated patients. The corresponding figures in the placebo group were 17% and 92%, respectively. CONCLUSION: One week of omeprazole treatment is a simple diagnostic test with a fairly high sensitivity. The specificity is poor owing to the placebo effect and to the lack of a gold standard in diagnosing reflux disease.

Anti-Ulcer Agents↗
PubMed1997

[A new surgical technique in atrial fibrillation. The maze procedure restores sinus rhythm].

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and increased mortality, partly due to the increased risk of stroke. The maze procedure, introduced by James Cox of the USA, is an internationally established surgical alternative in cases of unsuccessful medical or catheterised treatment of paroxysmal or chronic AF. It is an open heart procedure, involving multiple transmural incisions and continuous suture lines in both atria. By creating a maze of atrial tissue, the re-entrant circuits causing the AF are interrupted, hence re-establishing regular sinus rhythm and atrioventricular synchronization. The article reviews the initial 3-year experience of the procedure in 10 patients with AF, either paroxysmal (n = 5) or chronic (n = 5). The indications for surgery were disabling symptoms in all 10 cases, medical treatment failure in nine cases, previous AF-associated stroke in three cases, and a significant atrial septal defect in one case. All patients underwent extensive investigation both pre- and post-operatively. Postoperatively, nine of the 10 patients manifested regular sinus or atrial rhythm and freedom from or amelioration of preoperative symptoms associated with AF. There were no deaths, neurological complications or long-term recurrence of arrhythmia. One patient had an early recurrence of AF that was not amenable to medical treatment, and was subsequently treated with His' bundle ablation. Of the remaining nine patients, seven manifested signs of some postoperative atrial contraction at echocardiography, the occurrence of which needs to be borne in mind with a view to reducing the risk of future thromboembolic events. We recommend the maze procedure as an attractive surgical option in cases of unsuccessful medical treatment of paroxysmal or chronic AF.

Adult↗
PubMed1997

In vitro endothelialisation of arteriovenous loop grafts for haemodialysis.

OBJECTIVES: To evaluate the feasibility in a pilot study of in vitro endothelialisation of PTFE grafts used as interposition arteriovenous fistulas in uraemic patients. METHODS: Autologous saphenous vein endothelial cells were harvested and cultured on PTFE grafts in seven patients undergoing maintenance haemodialysis. The patients had several previous failures of vascular access sites. The patients were followed with duplex ultrasound, clinical examination and in one case an explanted graft was examined. RESULTS: At the end of follow-up four of the seven patients had patent grafts. One patient occluded the graft immediately postoperatively and another after 3.5 months. The former patient received a second endothelialised graft. In two further patients revision of the outflow was performed. In two patients a functioning graft was excised, in one case because of bleeding of a venous aneurysm and in one case because of suspected infection. The former which was excised 5 weeks postoperatively revealed that 85% of the surface was covered by endothelial cells. CONCLUSIONS: This pilot study shows that in vitro endothelialisation of PTFE grafts used for haemodialysis is possible in uraemic patients. In this highly problematic patient group the results are promising with endothelial cell coverage after 5 weeks of implantation.

Aged↗
PubMed1997

Antibiotic resistance in Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes in respiratory tract infections in outpatients.

Sensitivity patterns of Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes were studied prospectively in an outpatient population seeking medical advice for respiratory tract infections (RTI) in the Southern parts of Stockholm. In total, 3,214 nasopharyngeal and 1,907 throat swabs were cultured during January-February 1996. 32% of the patients had received antibiotics during the previous year. Reduced penicillin sensitivity in S. pneumoniae was rare (1.3%) and only seen in patients treated with antibiotics during the previous 4 months. Beta-lactamase production in H. influenzae was found in 13.4% of patients who had been treated with antibiotics during the last 4 months and in 7.9% of the others. No resistance (< 1%) to erythromycin was seen in S. pyogenes. In this population-based surveillance, the levels of resistance in common respiratory tract pathogens were thus low and correlated to previous antibiotic treatment. Strict indications for antibiotic treatment in uncomplicated RTI are advocated to maintain a low resistance rate. Penicillin is still the drug of choice in patients without frequent recurrences of RTI in a setting similar to the one studied.

Adolescent↗
PubMed1996

Secretion of prostacyclin, tissue plasminogen activator and its inhibitor by cultured adult human endothelial cells grown on different matrices.

OBJECTIVES: The aim of this study was to investigate the secretion of prostacyclin (PGI2), tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI- 1) produced by human great saphenous vein endothelial cells (HSVECs) in vitro when seeded to confluency on different matrices. METHODS: The matrices compared were: uncoated plastic, gelatin, collagen type-I gel, fibronectin, fibrin glue, de-endothelialized porcine aorta and ePTFE vascular grafts pre-coated with collagen type-I or human serum. RESULTS: There were no significant differences between basal production of PGI2 on the different matrices. The HSVECs responded with a significant increase in PGI2 secretion after stimulation with thrombin on all matrices, including the ePTFE grafts. A statistically significant higher secretion of tPA secretion was found in supernatants from cells cultured on collagen type-I gel. Interestingly, tPA secretion was lower by cells seeded on both collagen type-I and serum precoated ePTFE as compared to collagen type-1 gel. PAI-1 secretion however was significantly higher on collagen type-1 gel, gelatin, fibrin glue and porcine aorta but not on pre-coated ePTFE grafts. CONCLUSIONS: The findings emphasise the important effect of the matrix on endothelial secretion of PGI2, tPA and PAI-1. Differences in patency after implantation of in vitro endothelialized grafts, may be due to cellular function depending on the types of graft and matrix chosen.

Adult↗