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1.
  • Anwaar, I., et al. (author)
  • Intraplatelet cyclic 3'-5' guanosine monophosphate is related to serum cholesterol
  • 1996
  • In: International Angiology. - 0392-9590. ; 15:3, s. 201-206
  • Journal article (peer-reviewed)abstract
    • Nitric oxide (NO) exerts its vasodilator and antiaggregatory effects through activation of soluble guanylate cyclase and the consequent increase in the concentration of cGMP in target cells. We conducted this study in order to evaluate relationships between intraplatelet cGMP levels and risk factors for atherosclerosis in middle aged subjects. Intraplatelet cGMP was determined by radioimmunoassay and related to age, BMI, blood pressure, antihypertensive treatment, total, LDL and HDL cholesterol, triglycerides, blood glucose, HbA1c, smoking habit and intimal thickness of the common carotid artery in 265 subjects participating in a health survey (age 59 ± 6 years, range 48-68 years, 121 females, 144 males). Intraplatelet cGMP concentration was inversely correlated with total serum cholesterol (r = -0.18; p < 0.01) and HDL cholesterol (r = -0.14, p < 0.05) as well as with platelet count (r = -0.29; p < 0.001). When platelet count was adjusted for, only the correlation between total serum cholesterol and cGMP remained significant. No significant correlations could be demonstrated between intraplatelet cGMP levels and measurable parameters of atherosclerosis. Lower levels of the vasodilating and antiaggregating mediator cGMP in platelets are related to higher levels of serum total cholesterol. These results favour the hypothesis of a relationship between lipid levels and NO associated vasodilator and antiaggregating fuction in atherosclerosis.
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2.
  • Garson, J. A., et al. (author)
  • Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis
  • 1997
  • In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 4:5, s. 325-331
  • Journal article (peer-reviewed)abstract
    • Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.
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4.
  • Wallmark, A, et al. (author)
  • Feasibility of extracorporeal on-line large-scale plasma adsorptions on protein A-sepharose columns in cancer patients
  • 1984
  • In: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 8:1, s. 72-81
  • Journal article (peer-reviewed)abstract
    • The feasibility of extracorporeal adsorption of 1.5-3 L plasma on protein A-Sepharose was investigated in six patients with advanced cancer. Anticoagulation with heparin was associated with respiratory distress syndrome in two patients, most likely caused by complement activation as indicated by a transient leukopenia during plasma reinfusion and appearance of C3 degradation products in the extracorporeal circulation. Addition of citrate abolished the respiratory symptoms, C3 degradation, and leukopenia, and no adverse reactions were observed. No objective tumor regression was observed in any of the patients. Three patients progressed during therapy. In one of these, multifocal central tumor necrosis was observed as a possible, although unproven, therapeutic effect. Increased natural killer and/or killer cell activities were recorded in three patients and increased complement-dependent serum cytotoxicity in one patient. The level of circulating immune complexes decreased significantly (18-28%) in three patients studied. It is concluded that extracorporeal plasma adsorption on protein A-Sepharose is feasible when citrate is added to the extracorporeal system, but its therapeutic efficacy is uncertain.
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5.
  • Brahme, A., et al. (author)
  • Evaluation of a GEM and CAT-based detector for radiation therapy beam monitoring
  • 2000
  • In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 454, s. 136-141
  • Journal article (peer-reviewed)abstract
    • We are developing a radiation therapy beam monitor for the Karolinska Institute. This monitor will consist of two consecutive detectors confined in one gas chamber: a keV-photon detector, which will allow diagnostic quality visualization of the patient, and a MeV-photon detector, that will measure the absolute intensity of the therapy beam and its position with respect to the patient. Both detectors are based on highly radiation resistant gas and solid photon to electron converters, combined with GEMs and a CAT as amplification structures. We have performed systematic studies of the high-rate characteristics of the GEM and the CAT, as well as tested the electron transfer through these electron multipliers and various types of converters. The tests show that the GEM and the CAT satisfy all requirements for the beam monitoring system. As a result of these studies we successfully developed and tested a full section of the beam monitor equipped with a MeV-photon converter placed between the GEM and the CAT.
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6.
  • Graham, J. B., et al. (author)
  • The Malmo polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms
  • 1988
  • In: American Journal of Human Genetics. - 0002-9297. ; 42:4, s. 573-580
  • Journal article (peer-reviewed)abstract
    • A mouse monoclonal antibody (MAB 9,9) to coagulation factor IX (F.IX) detects a polymorphism in the plasma of normal people. Its epitope has been narrowed down to <6 amino acids in the activation peptide of the X-linked F.IX protein. The activation peptide contains a dimorphism - Thr:Ala - at position 148 of the protein. Using synthetic oligonucleotides, we have demonstrated that (1) the F.IX which reacts with 9.9 has Thr at position 148 and (2) that which does not has Ala. Positive reactors (148(thr)) are designated Malmo A, and negative reactors (148(ala)) are designated Malmo B. The plasma levels of AA women are indistinguishable from those of A men, and both B men and BB women are null against MAB 9.9. The plasma level of Malmo A in AB women is approximately half that of AA women, and 'lyonization' is clearly operating in the heterozygotes. The dimorphism is in strong linkage disequilibrium with two other intragenic RFLPs, TaqI and XmnI. Furthermore, intragenic crossing-over - including double crossing-over - appears to have occurred between the three sites. Seven of the eight possible haplotypes have been identified, five in men and two others in women. The immunoassay that identifies ~50% of the AB women in the pool of Malmo A females with 95% confidence identifies men unambiguously as A or B. The assay would be very useful for population-genetic studies of the Malmo epitope if the studies were limited to men.
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7.
  • Ljung, R., et al. (author)
  • Two allotypes of factor IX present in haemophilia B
  • 1986
  • In: Scandinavian Journal of Haematology. - : Wiley. - 0036-553X. ; 37:5, s. 411-416
  • Journal article (peer-reviewed)abstract
    • Factor IX antigen (IX:Ag) was measured with three different immunoradiometric assays (IRMAs) in 30 healthy people and 43 patients with haemophilia B of varying severity. Two of the IRMAs were based on monoclonal antibodies capable of differentiating between two genetically determined molecular variants of normal factor IX. Most patients with severe hemophilia B lacked demonstrable IX:Ag. The factor IX variant that is undetectable with one of the monoclonal antibodies used was present in 2 out of 6 families with moderate haemophilia B and in 1 out of 6 families with mild haemophilia B. The existence of allotypes of factor IX in hemophilia B may have practical implications for carrier detection and prenatal diagnosis.
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8.
  • Sun, Yongxin, et al. (author)
  • Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease.
  • 2003
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:3, s. 136-144
  • Journal article (peer-reviewed)abstract
    • It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha1-antichymotrypsin (ACT), alpha1-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
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9.
  • Wallmark, A., et al. (author)
  • Determination of factor IX allotypes for carrier identification in haemophilia B
  • 1987
  • In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 67:4, s. 427-432
  • Journal article (peer-reviewed)abstract
    • The existence of two genetic variants (allotypes) of normal human factor IX is used for carrier detection in three families with severe and one with mild haemophilia B. By analysis of IX:Ag with two different monoclonal antibodies in 93 members of the families, allelic assignment is shown to be a complement in carrier diagnosis to genotypic DNA studies. Allelic assignment makes possible a reliable diagnosis based on phenotypic studies, though its usefulness is limited due to ethnic variation in allelic frequency. Determination of factor IX allotypes should be useful for carrier detection in any Swedish families with haemophilia B.
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10.
  • Wallmark, M., et al. (author)
  • Operating range of a gas electron multiplier for portal imaging
  • 2001
  • In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 471:02-jan, s. 151-155
  • Journal article (peer-reviewed)abstract
    • At the Karolinska Institute in Stockholm, Sweden a new detector for portal imaging is under development, which could greatly improve the alignment of the radiation beam with respect to the tumor during radiation treatment. The detector is based on solid converters combined with gas electron multipliers (GEMs) as an amplification structure. The detector has a large area and will be operated in a very high rate environment in the presence of heavy ionizing particles. As was discovered recently high rates and alpha particles could cause discharges in GEM and discharge propagation from GEM to GEM and to the readout electronics. Since reliability is one of the main requirements for the portal imaging device, we performed systematic studies to find a safe operating range of the device, free from typical high rate problems, such as discharges.
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