Biomedical subjects

T Nilsson

Publications and source records attributed to T Nilsson.

At least 37 records · Page 2Linked to original sources

PubMed2002

Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation.

Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.

Adult↗

PubMed2002

Negative spiral CT in acute pulmonary embolism.

PURPOSE: To retrospectively evaluate the clinical outcome of non-anticoagulated patients with clinically suspected acute pulmonary embolism (PE) and no symptoms or signs of deep venous thrombosis (DVT) following a negative contrast medium-enhanced spiral CT of the pulmonary arteries (s-CTPA). MATERIAL AND METHODS: During a 24-month period, 739 of 751 patients underwent s-CTPA with acceptable diagnostic quality for clinically suspected acute PE. All patients who had a CT study not positive for PE were followed up with a questionnaire, a telephone interview and review of all medical reports, including autopsies and death certificates for any episodes of venous thromboembolism (VTE) during a 3-month period. RESULTS: PE was diagnosed in 158 patients. Of the remaining 581 patients with a negative s-CTPA, 45 patients were lost to follow-up. 88 patients were excluded because of anticoagulation treatment (cardiac disorder n=32, chronic VTE or acute symptomatic DVT n=31, PE diagnosed at pulmonary angiography n=1, thrombus prophylaxis during diagnostic work-up or other reasons than VTE n=24) and 7 patients undergoing lower extremity venous studies because of symptoms of DVT (all negative). Thus, 441 patients with a negative s-CTPA and no DVT symptoms, venous studies or anticoagulant treatment constituted the follow-up cohort. Four of these patients had proven VTE (all PE) during the 3-month follow-up period. Two of the PE episodes contributed to the patient's death. CONCLUSION: Patients with clinically suspected acute PE, no symptoms or signs of DVT and a negative single slice s-CTPA using 3-5 mm collimation, may safely be left without anticoagulation treatment unless they are critically ill, have a limited cardiopulmonary reserve and/or if a high clinical suspicion remains.

Adult↗

PubMed2001

Sorting of Golgi resident proteins into different subpopulations of COPI vesicles: a role for ArfGAP1.

We present evidence for two subpopulations of coatomer protein I vesicles, both containing high amounts of Golgi resident proteins but only minor amounts of anterograde cargo. Early Golgi proteins p24alpha2, beta1, delta1, and gamma3 are shown to be sorted together into vesicles that are distinct from those containing mannosidase II, a glycosidase of the medial Golgi stack, and GS28, a SNARE protein of the Golgi stack. Sorting into each vesicle population is Arf-1 and GTP hydrolysis dependent and is inhibited by aluminum and beryllium fluoride. Using synthetic peptides, we find that the cytoplasmic domain of p24beta1 can bind Arf GTPase-activating protein (GAP)1 and cause direct inhibition of ArfGAP1-mediated GTP hydrolysis on Arf-1 bound to liposomes and Golgi membranes. We propose a two-stage reaction to explain how GTP hydrolysis constitutes a prerequisite for sorting of resident proteins, yet becomes inhibited in their presence.

ADP-Ribosylation Factor 1↗

PubMed2001

Identification of rabaptin-5, rabex-5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER.

The role of rab33b, a Golgi-specific rab protein, was investigated. Microinjection of rab33b mutants stabilised in the GTP-specific state resulted in a marked inhibition of anterograde transport within the Golgi and in the recycling of glycosyltransferases from the Golgi to the ER, respectively. A GST-rab33b fusion protein stabilised in its GTP form was found to interact by Western blotting or mass spectroscopy with Golgi protein GM130 and rabaptin-5 and rabex-5, two rab effector molecules thought to function exclusively in the endocytic pathway. A similar binding was seen to rab1 but not to rab6, both Golgi rabs. In contrast, rab5 was as expected, shown to bind rabaptin-5 and rabex-5 as well as the endosomal effector protein EEA1 but not GM130. No binding of EEA1 was seen to any of the Golgi rabs.

Animals↗

PubMed2001

[A controlled trial with prolonged follow up: percutaneous intervention in acute myocardial infarction is equivalent to thrombolytic therapy].

Previous studies comparing percutaneous coronary intervention (PCI) with thrombolysis for treatment of myocardial infarction with ST-elevation have in meta-analyses but not in randomized trials shown that PCI is more effective. Despite a large volume of primary PCI performed in Sweden no controlled trials have been carried out. The present study included 96 patients with myocardial infarction with ST-segment elevation treated with primary PCI 1995-1998. The main indications were shock (15 cases), contraindication to thrombolysis (24 cases), as an alternative to thrombolysis (57 cases), with a mortality in the respective groups of 67, 25 and 10 percent. Controls matched for age and infarct location and treated with thrombolysis could be identified for 55 of the patients treated with PCI. After four years 40 percent and 52 percent of the patients treated with PCI and thrombolysis respectively reached the combined endpoint of death/myocardial infarction/revascularization/angina pectoris (not significant). In conclusion, the study shows that primary PCI in patients with myocardial infarction with ST-segment elevation can be performed safely also in Sweden.

Aged↗

PubMed2001

[Curative treatment of ventricular cancer].

Extended lymphadenectomy on connection with the surgical treatment of gastric cancer is gaining access in western centres especially since Japanese centres have shown an ever increasing rate of survival over several decades, coupled with the fact that operative procedures have become more sophisticated. The latest prospective studies in the west seem to confirm the value of lymphadenectomy in some patients. Furthermore, correct staging demands extended lymphadenectomy. For patients with gastric cancer, adjuvant preoperative chemotherapy is probably an asset.

Chemotherapy, Adjuvant↗

PubMed2001

[Policy document. Catheter-based diagnosis and treatment of coronary diseases].

Diagnostic coronary angiography and percutaneous coronary interventions (PCI) are rapidly developing fields. In-house thoracic surgery backup is no longer a prerequisite for PCI. The demand for physicians trained in interventional cardiology has created a need to formalise such education. The Swedish societies of cardiology and thoracic radiology have agreed on a policy document establishing the details of this education. It is the responsibility of the tutor to decide when the pupil has achieved adequate skills.

Angioplasty, Balloon, Coronary↗

PubMed2001

Halo structure of (14)Be.

The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.

Journal Article↗

PubMed2001

The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.

Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during dalteparin treatment. These findings suggest that dalteparin could be substituted for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.

Anticoagulants↗

PubMed2001

Chlorite dismutase from Ideonella dechloratans.

Chlorite dismutase has been purified from the chlorate-metabolizing bacterium Ideonella dechloratans. The purified enzyme is tetrameric, with a relative molecular mass of 25,000 for the subunit, and contains about 0.6 heme/subunit as isolated. Its catalytic properties are similar, but not identical, to those found for a similar enzyme purified earlier from the bacterium GR-1. The heme group in Ideonella chlorite dismutase is readily reduced by dithionite, in contrast to the GR-1 enzyme, and redox titration gave a value of -21 mV for the midpoint potential at pH 7. The heme group has been characterized by optical and EPR spectroscopy. It is high-spin ferric at neutral pH, with spectroscopic properties similar to those found for cytochrome c peroxidase. In the alkaline pH range, a low-spin compound is formed. A 22-residue N-terminal amino acid sequence has been determined and no homologue has been found in the protein sequence databases.

Amino Acid Sequence↗

PubMed2001

Geographical differences in the incidence of acute myocardial infarction in Sweden. Analyses of possible causes using two parallel case-control studies.

OBJECTIVES: To analyse differences in myocardial infarction incidence between two Swedish counties and to evaluate the importance of major risk factors for the observed differences. DESIGN: The incidence of first myocardial infarction was studied using information from registers. For a number of risk factors of myocardial infarction, the prevalence as well as the relative risk was estimated from population controls of case-control studies in the two areas. SUBJECTS: Men and women aged 45-64 years in Stockholm and Västernorrland County 1993-94. MAIN OUTCOME MEASURES: Relative risks (RRs) and impact fractions were used to evaluate the importance of differences in risk factor prevalence for differences in myocardial infarction incidence between the two areas. RESULTS: The incidence of first myocardial infarction was higher in Västernorrland than in Stockholm amongst both men (RR = 1.23; 95% CI = 1.08-1.40) and women (RR = 1.41; 95% CI = 1.11-1.79). Obesity and increased levels of blood serum lipids were more prevalent in Västernorrland than in Stockholm amongst men with impact fractions of 6 and 9-11%, respectively. Amongst women, corresponding differences were not seen, but job strain and shift work tended to be more common in the more northern area. Current smoking was more frequent in Stockholm, particularly for women. CONCLUSIONS: The incidence of first myocardial infarction was higher in Västernorrland than in Stockholm in both genders. A higher prevalence of obesity and elevated blood serum lipids may explain, in part, this excess incidence amongst men, but amongst women the causes of the higher incidence in the more northern area remain largely unclear.

Aged↗

PubMed2001

Value of structured clinical and scintigraphic protocols in acute pulmonary embolism.

PURPOSE: To study the use of a combination of a clinical and scintigraphic protocol in relation to the final outcome diagnosis in patients with clinical suspicion of acute pulmonary embolism (PE). MATERIAL AND METHODS: A total of 170 patients with clinical suspicion of acute PE were all examined with ECG, blood chemistry, chest X-ray, pulmonary scintigraphy and selective pulmonary arteriography. The scintigraphic and clinical probabilities of PE were estimated on visual analogue scales (VASs) by different readers unaware of each others' results. The follow-up time was 6 months. In order to establish the final diagnosis a final outcome committee was created. They analysed in retrospect all the clinical and laboratory data and established whether the patient had had PE or not. RESULTS: The final outcome committee concluded that 53 patients had PE. When the scintigraphic and clinical probability judgements were congruent, a combined probability of 1-25% (i.e low probability) had a negative predictive value of 98%. When the combined probability was 26-75% (i.e. intermediate) half of the cases had PE. With a combined probability of 76-100% (i.e. high) the positive predictive value was 100%. CONCLUSION: By applying a model of combined clinical and scintigraphic probabilities for PE, the diagnosis is ruled in when the combined probability is high, and ruled out when the combined probability is low. However, nearly half of the patients will still have an uncertain diagnosis for which further diagnostic procedures may be allocated.

Adult↗

PubMed2001

Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins.

Addition of the weak base ammonium chloride (NH4Cl) or the proton pump inhibitor bafilomycin A1 to cultured HeLa and LS 174T cells effectively neutralized the pH gradient of the secretory pathway. This resulted in relocalization of the three studied glycosyltransferases, N-acetylgalactosaminyltransferase 2, beta1,2 N-acetylglucosaminyltransferase I, and beta1,4 galactosyltransferase 1, normally localized to the Golgi stack, the medial/trans-Golgi and the trans-Golgi/TGN, respectively. Indirect immunofluorescence microscopy, immunoelectron microscopy, and subcellular fractionation of the tagged or native glycosyltransferases showed that NH4Cl caused a relocalization of the enzymes mainly to vesicles of endosomal type, whereas bafilomycin A1 gave mainly cell surface staining. The general morphology of the endoplasmic reticulum and Golgi apparatus was retained as judged from immunofluorescence and electron microscopy studies. When the O-glycans on the guanidinium chloride insoluble gel-forming mucins from the LS 174T cells were analyzed by gas chromatography-mass spectrometry after neutralization of the secretory pathway pH by NH4Cl over 10 days shorter O-glycans were observed. However, no decrease in the number of oligosaccharide chains was indicated. Together, the results suggest that pH is a contributing factor for proper steady-state distribution of glycosyltransferases over the Golgi apparatus and that altered pH may cause alterations in glycosylation possibly due to a relocalization of glycosyltransferases.

Ammonium Chloride↗

PubMed2001

The influence of curli, a MHC-I-binding bacterial surface structure, on macrophage-T cell interactions.

Escherichia coli express thin surface fimbriae called curli which bind soluble matrix proteins and major histocompatibility complex (MHC)-I molecules. The present study addressed the ability of purified curli or curliated E. coli to influence peptide presentation on MHC-I, T cell proliferation and bacterial uptake by macrophages. In vitro studies with curli-proficient E. coli YMel and the isogenic curli-deficient strain YMel-1, both expressing the model antigen Crl-OVA, showed that curli expression by E. coli does not appear to influence the efficiency by which the bacteria are processed by murine macrophages for OVA(257-264) presentation on K(b). Furthermore, curli expression by E. coli did not influence the binding of exogenously added OVA(257-264) peptide to K(b) on the surface of prefixed macrophages. In addition, neither curliated nor non-curliated heat-killed bacteria influenced proliferation of either murine or human T cells stimulated with anti-CD3. Finally, curliated E. coli adhered to and were internalized by macrophages from C57BL/6 and MHC-I-deficient TAP1(-/-) mice equally well. Together these studies show that curli expression by E. coli does not appear to influence phagocytic processing of bacteria expressing Crl-OVA for OVA(257-264)/K(b) presentation, the binding of exogenously added OVA(257-264) to K(b) or T cell proliferation. In addition, although curli expression by E. coli enhances bacterial interaction with macrophages, curli interaction with MHC-I does not significantly contribute to this adherence.

Animals↗

PubMed2001

Promoter-proximal regulatory elements involved in oriP-EBNA1-independent and -dependent activation of the Epstein-Barr virus C promoter in B-lymphoid cell lines.

The identification of the cellular factors that control the transcription regulatory activity of the Epstein-Barr virus C promoter (Cp) is fundamental to the understanding of the molecular mechanisms that control virus latent gene expression. Using transient transfection of reporter plasmids in group I phenotype B-lymphoid cells, we have previously shown that the -248 to -55 region (-248/-55 region) of Cp contains elements that are essential for oriPI-EBNA1-dependent as well as oriPI-EBNA1-independent activation of the promoter. We now establish the importance of this region by a detailed mutational analysis of reporter plasmids carrying Cp regulatory sequences together with or without oriPI. The reporter plasmids were transfected into group I phenotype Rael cells and group III phenotype cbc-Rael cells, and the Cp activity measured was correlated with the binding of candidate transcription factors in electrophoretic mobility shift assays and further assessed in cotransfection experiments. We show that the NF-Y transcription factor interacts with the previously identified CCAAT box in the -71/-63 Cp region (M. T. Puglielli, M. Woisetschlaeger, and S. H. Speck, J. Virol. 70:5758-5768, 1996). We also show that members of the C/EBP transcription factor family interact with a C/EBP consensus sequence in the -119/-112 region of Cp and that this interaction is important for promoter activity. A central finding is the identification of a GC-rich sequence in the -99/-91 Cp region that is essential for oriPI-EBNA1-independent as well as oriPI-EBNA1-dependent activity of the promoter. This region contains overlapping binding sites for Sp1 and Egr-1, and our results suggest that Sp1 is a positive and Egr-1 is a negative regulator of Cp activity. Furthermore, we demonstrate that a reporter plasmid that in addition to oriPI contains only the -111/+76 region of Cp still retains the ability to be activated by EBNA1.

B-Lymphocytes↗

PubMed2001

A case-referent study of cancer mortality among sulfate mill workers in Sweden.

OBJECTIVES: To investigate whether workers in Swedish sulfate mills have an increased risk of death from certain malignancies that have previously been linked to the pulping process. METHODS: Subjects of the study (n=2480) were men aged 40-75 at death during 1960-89 in the parishes surrounding four sulfate mills. Exposure assessment was based on information from the personnel files in the mills- 35% of the subjects were recognised there, and work categories were created. RESULTS: Among all sulfate mill workers, the odds ratio (OR) (90% confidence interval (90% CI)) for death from lung cancer was 1.6 (1.1 to 2.3), pleural mesotheliomas 9.5 (1.9 to 48), brain tumours 2.6 (1.2 to 5.3), and liver or biliary tract cancer 2.3 (1.0 to 5.2). There was an increased mortality from leukaemia among workers in the soda recovery plant (5.9 (2.6 to 13)) and bleaching plant and digester house (2.8 (1.0 to 7.5)). CONCLUSIONS: Sulfate mill workers were at increased risk of dying from lung cancer and pleural mesotheliomas, probably due to exposure to asbestos. Increased risks of brain tumours and cancers of the liver or biliary tract were also found but the aetiology is not obvious.

Adult↗

PubMed2001

Quantitative thermal perception thresholds relative to exposure to vibration.

OBJECTIVES: To assess the risk of disturbed thermal perception relative to exposure to vibration, to investigate a possible exposure-response relation and to analyse a possible relation between thermal perception and sensory symptoms. METHODS: The study was based on a cross section of 123 male workers exposed to vibration and 62 male workers who were not exposed. Thermal perception of cold, warmth, and heat pain was bilaterally determined from the thenar eminence by the method of limits. Perception of cold and warmth were also tested in the second digit. Personal energy equivalent exposure to vibration was measured for all subjects. Vibration was measured in accordance with International Standards Organisation (ISO) 5349 and assessed separately for the left and right hand. RESULTS: Combining exposure times and intensities gave the left hand an 0.80 exposure to vibration compared with the right. The risk of having contracted reduced thermal perception was increased at all test sites. The risk was higher for the thenar measurements than the finger measurements. A yearly extra contribution of 4000 mh/s(2) in cumulative exposure increases the risk of contracting a wider neutral zone by 18% (95% confidence interval (95% CI) 1.06 to 1.32) for the right and 18% (1.05 to 1.32) for the left hand side. Subjects with symptoms of nocturnal paraesthesia had a rate ratio (95% CI) of 2.80 (1.17 to 6.67) for the right hand and 2.72 (1.12 to 6.63) for the left hand for increased neutral zones at the thenar eminence. CONCLUSIONS: The results indicate thermal sensory impairment related to cumulative exposure to vibration. The effect appeared at vibration levels below the current guiding standard. Quantitative sensory testing of thermal perception offers the chance to assess this specific hazard to the peripheral sensorineural system associated with hand intensive work entailing vibration.

Adult↗

PubMed2001

Resection of a giant left main stem coronary artery aneurysm.

A 2 cm in diameter aneurysm of the left main stem was diagnosed in 1979. The aneurysm increased to 10 cm in diameter during 20 years. It was resected and successful bypass surgery was performed. No previous report was found of a giant true aneurysm involving the left main stem.

Coronary Aneurysm↗